methylcellulose and ethyl-cellulose

This review highlights references where ethylcellulose, methylcellulose and hypromellose were used to make microcapsules. The review has been divided into three parts. This first part discusses various materials used to formulate microcapsules, such as the three encapsulating polymers as well as protective colloids, plasticizers and surfactants. The second part covers the various techniques used to make microcapsules, such as temperature-induced phase separation, emulsion solvent evaporation, solvent evaporation, film coating, and others. The third part covers the various applications for which microcapsules are used, such as modified release, improved efficacy and safety, taste- and odor-masking, and others. It is hoped that formulators can use Part 1 as a guide to the literature documenting formulation of microcapsules made from these encapsulating polymers. SciFinder was utilized to identify the pertinent literature. SciFinder leverages literature databases, such as Chemical Abstracts Service Registry and Medline. A total of 379 references were identified during the review. The need for a three-part review reflects the extensive amount of literature identified concerning these three encapsulating polymers.

Topics: Capsules; Cellulose; Delayed-Action Preparations; Drug Compounding; Humans; Hypromellose Derivatives; Methylcellulose; Particle Size

This three-part review has been developed following the evaluation of literature where ethylcellulose, methylcellulose, or hypromellose was used to make microcapsules. Parts 1 and 2 of the review are published in separate papers. Part 1 covers the various materials used to formulate microcapsules, and Part 2 covers the various techniques used to make microcapsules. In the current paper, Part 3 covers the end-use applications for which microcapsules are used. Examples of applications to be covered include modified release, improved efficacy and safety, multiparticulate compression, improved processability and stability, and taste- and odor-masking. It is hoped that formulators can use Part 3 to understand the various end-use applications of microcapsules made from these encapsulating polymers. SciFinder was utilized to perform the literature search. SciFinder leverages literature databases, such as Chemical Abstracts Service Registry and Medline. A total of 379 references were identified during the review. The need for a three-part review reflects the extensive amount of literature identified concerning these three encapsulating polymers.

Topics: Capsules; Cellulose; Delayed-Action Preparations; Drug Compounding; Hydrogen-Ion Concentration; Hypromellose Derivatives; Kinetics; Methylcellulose; Models, Theoretical; Particle Size; Surface Properties

This three-part review has been developed following the evaluation of literature where ethylcellulose, methylcellulose or hypromellose was used to make microcapsules. Parts 1 and 3 of the review are published as separate papers. Part 1 covers the various materials used to formulate microcapsules, and Part 3 covers the various end-use applications for microcapsules. In the current paper, Part 2 covers the techniques used to make microcapsules. Examples of techniques to be covered include temperature-induced phase separation, emulsion solvent evaporation, solvent evaporation, film coating, nonsolvent addition and spray drying. It is hoped that formulators can use Part 2 to understand how to formulate microcapsules using these encapsulating polymers. SciFinder was utilized to perform the literature search. SciFinder leverages literature databases, such as Chemical Abstracts Service Registry and Medline. A total of 379 references were identified during the review. The need for a three-part review reflects the extensive amount of literature identified concerning these three encapsulating polymers.

Topics: Capsules; Cellulose; Drug Compounding; Hypromellose Derivatives; Methylcellulose; Particle Size; Surface Properties

In this study, once-daily, sustained-release matrix tablets of tolterodine l-tartrate (TOL) for treatment of overactive bladder (OAB) were prepared by direct compression using various amounts of hydrophilic polymers such as HPMC 2910 and HPMC 2208 along with other tablet excipients; the tablets were then coated. In vitro dissolution studies were carried out under different pH conditions. The dissolution data were fitted into zero-order, first-order, Higuchi and Korsemeyer-Peppas models to identify the pharmacokinetics and mechanism of drug release. Among the four formulations (F1-F4), the dissolution profiles of formulation F2 were most similar to the marketed product with similarity and difference factors of 70.25 and 1.59 respectively. Furthermore, pharmacokinetic studies were carried out in healthy human volunteers after oral administration of the prepared TOL sustained-release matrix-coated tablet and the marketed product. The results revealed that the pharmacokinetic parameters of AUC, Cmax, Tmax, t1/2, Kel, and MRT of TOL for the developed formulation (F2) were not significantly different from that for the marketed product, suggesting that they were bioequivalent. Therefore, the developed sustained-release tablet formulation of TOL could be an alternative dosage form to the SR capsule for treatment of OAB.

Topics: Benzhydryl Compounds; Cellulose; Cresols; Cross-Over Studies; Delayed-Action Preparations; Drug Administration Schedule; Drug Compounding; Excipients; Fatty Acids; Hardness; Humans; Hypromellose Derivatives; Methylcellulose; Phenylpropanolamine; Solubility; Tablets; Therapeutic Equivalency; Tolterodine Tartrate; Urological Agents

The purpose of this study is to increase the lag time and prevent release of budesonide, a corticosteroid drug used in Crohn's disease for the first 5 h and efficiently deliver it to the colon. Eudragit S100 spray-coated capsules and pulsatile systems using tablet plugs of cellulose acetate butyrate (CAB), HPMC K4M, guar gum, and pectin were prepared. Eudragit S100-coated capsules released 80.62% after 5 h. In pulsatile systems, decreasing the ratio of the polymer significantly increased the rate and extent of drug release. Spray-coating with EUD S100 decreased the extent of drug release to 48.41%, 69.94%, 80.58%, and 45.23% in CAB, HPMC K4M, pectin, and guar gum, respectively; however, the entire amount was released in the target area. In the presence of bacterial enzymes, selected formulas showed nearly 100% release. X-ray imaging performed to monitor the capsules throughout the GIT in human volunteers of the capsules and spray-coated pulsatile systems with 25% guar gum in the plug showed bursting in the transverse and ascending colon, respectively. Both formulations showed marked reduction in induced rabbit colitis model.

Topics: Administration, Oral; Adult; Animals; Biological Availability; Budesonide; Capsules; Cellulose; Chemistry, Pharmaceutical; Colitis; Colon; Colon, Transverse; Delayed-Action Preparations; Galactans; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Hypromellose Derivatives; Ileum; Lactose; Male; Mannans; Mannosidases; Methylcellulose; Pectins; Peroxidase; Plant Gums; Polygalacturonase; Polymethacrylic Acids; Rabbits; Radiography; Rectum; Stomach; Tablets; Trinitrobenzenesulfonic Acid; Young Adult

This study attempted to characterize the influence of core and coating formulations on the release profiles to establish in vitro/in vivo correlations of pulsatile pattern for a pulsatile drug delivery system activated by membrane rupture based on three core tablet formulations (A-core: HPMC 50+4000 cps, B-core: E10M, and C-core: K100M) coated with various thicknesses of a semipermeable ethylcellulose membrane plasticized with HPMC 606 (Pharmacoat 606) at different ratios with/without adding various amounts of water to dissolve it in the coating solution. Drug release behaviors were investigated using apparatus II in four media of pH 1.2 solution, pH 6.8 buffer, deionized water, and a NaCl solution rotated at 75, 100, and 150 rpm. Pilot studies of the in vivo pharmacokinetics were conducted as well for comparison with the in vitro results. Results demonstrated that drug release from the three kinds of core tablets in deionized water increased with an increasing stirring rate, and decreased with an increasing viscosity grade of HPMC used in the core formulations. A significant promotion of drug release from core tablets was observed for the three levels of NaCl media in comparison with that in deionized water. Results further demonstrated that a slightly slower release rate in pH 1.2 solution and a faster release rate in pH 6.8 buffer than that in deionized water were observed for the A-core and B-core tablets, with the former being slower than the latter. However, similar release rates in the three kinds of media were observed for C-core tablets, but they were slower than those for the A- and B-core tablets. Dissolution of coated tablets showed that the controlling membrane was ruptured by osmotic pressure and swelling which activated drug release with a lag time. The lag time was not influenced by the pH value of the release medium or by the rotation speeds. The lag time increased with a higher coating level, but decreased with the addition of the hydrophilic plasticizer, Pharmacoat 606, and of the water amount in the coating solution. The lag time also increased with a higher concentration of NaCl in the medium. The release rate after the lag time was determined by the extent of retardation of gelation of HPMC in the core tablet based on the ionic strength of the medium. Results of the three pilot crossover studies for the exemplified pulsatile systems indicated that the lag time for the in vivo plasma profile was well correlated with that determined fr

Topics: Administration, Oral; Adult; Cellulose; Chemistry, Pharmaceutical; Cross-Over Studies; Delayed-Action Preparations; Doxazosin; Drug Carriers; Humans; Hydrogen-Ion Concentration; Hypromellose Derivatives; Membranes, Artificial; Methylcellulose; Models, Biological; Osmotic Pressure; Permeability; Pilot Projects; Pulse Therapy, Drug; Sodium Chloride; Solubility; Tablets; Viscosity; Water

The buccal region offers an attractive route of administration for systemic drug delivery. Carvedilol (dose, 3.125-25 mg) is beta-adrenergic antagonist. Its oral bioavailability is 25-35% because of first pass metabolism. Buccal absorption studies of a carvedilol solution in human volunteers showed 32.86% drug absorption. FTIR and UV spectroscopic methods revealed that there was no interaction between carvedilol and polymers. Carvedilol patches were prepared using HPMC, carbopol 934, eudragit RS 100, and ethylcellulose. The patches were evaluated for their thickness uniformity, folding endurance, weight uniformity, content uniformity, swelling behaviour, tensile strength, and surface pH. In vitro release studies were conducted for carvedilol-loaded patches in phosphate buffer (pH, 6.6) solution. Patches exhibited drug release in the range of 86.26 to 98.32% in 90 min. Data of in vitro release from patches were fit to different equations and kinetic models to explain release profiles. Kinetic models used were zero and first-order equations, Hixon-Crowell, Higuchi, and Korsmeyer-Peppas models. In vivo drug release studies in rabbits showed 90.85% of drug release from HPMC-carbopol patch while it was 74.63 to 88.02% within 90 min in human volunteers. Good correlation among in vitro release and in vivo release of carvedilol was observed.

Topics: Acrylates; Acrylic Resins; Administration, Buccal; Adrenergic beta-Antagonists; Adult; Animals; Carbazoles; Carvedilol; Cellulose; Chemistry, Pharmaceutical; Dosage Forms; Drug Carriers; Drug Compounding; Drug Stability; Drug Storage; Humans; Hydrogen-Ion Concentration; Hypromellose Derivatives; Male; Methylcellulose; Mouth Mucosa; Propanolamines; Rabbits; Solubility; Surface Properties; Technology, Pharmaceutical; Tensile Strength; Viscosity

We have developed a 200 mg and 400 mg sustained-release sodium valproate tablet that allows effective blood concentration of the active drug with once-a-day dosing. The controlled dissolution or sustained release of the drug was attained by a membrane-controlled system. A single-coating system did not adequately control the dissolution rate, and therefore double-coated tablets were prepared and a human pharmacokinetic study was conducted. With the 200 mg VPA-Na tablets, the nonfasting C(max) was only 20% higher than the fasting C(max). An in vitro dissolution test was conducted to predict the effects of food on drug dissolution after administration of this tablet. A relatively good correlation was observed between the absorption profiles and the dissolution profiles of the drug.

Topics: Acrylic Resins; Anticonvulsants; Area Under Curve; Cellulose; Cross-Over Studies; Delayed-Action Preparations; Dose-Response Relationship, Drug; Fasting; Humans; Hypromellose Derivatives; Methylcellulose; Postprandial Period; Solubility; Tablets; Valproic Acid

The bioavailability of ibuprofen from hot-melt extruded mini-matrices based on ethyl cellulose and a hydrophilic excipient was tested. During the in vivo evaluation an oral dose of 300 mg ibuprofen was administered to healthy volunteers (n = 9) in a randomized cross-over study and compared with a commercially available sustained release product (Ibu-slow). The plasma samples were analysed by a validated HPLC-UV method. One mini-matrix formulation (F-1) consisted of 30% ibuprofen, 35% ethyl cellulose and 35% hydroxypropyl methylcellulose (Metolose 60 SH 50), while the second formulation (F-2) contained 60% ibuprofen, 20% ethyl cellulose and 20% xanthan gum. These mini-matrices were administered in hard gelatine capsules. Both formulations behaved in vivo as sustained release formulations with an HVD(t50% Cmax) value (time span during which the plasma concentration is at least 50% of the Cmax value) of 7.6 and 12.0 h for formulations F-1 and F-2, respectively, whereas a value of 5.2 h was obtained for Ibu-slow. Although a significantly higher Cmax and AUC(0-24 h) was seen for the reference product, the relative bioavailability of both experimental formulations was about 80%.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Biological Availability; Capsules; Cellulose; Chromatography, High Pressure Liquid; Cross-Over Studies; Delayed-Action Preparations; Drug Carriers; Female; Humans; Hypromellose Derivatives; Ibuprofen; Male; Methylcellulose; Middle Aged; Polysaccharides, Bacterial; Solubility

Oleogels,gels in which the continuous liquid phase is oil, have been suggested as promising low-saturated alternatives to the conventional shortenings. In this study, we aimed to develop and optimize low saturated oleogel shortenings using ethylcellulose or ethylcellulose/hydroxypropyl methylcellulose biopolymers (as oleogelators), sunflower oil (as the base oil), and palm stearin (as the source of saturated fatty acids). Using the response surface-d-optimal method, oleogel formulations containing saturated fatty acids as low as 15.19 % could be developed. As compared to the commercial shortening samples, oleogel shortenings had much lower saturation levels (15.19-17.02 vs 47.87-58.65 %) but a comparable melting point, firmness, and rheological properties. However, oleogel samples had lower solid fat content and induction period of oxidation than commercial ones. Oleogel made using ethylcellulose/hydroxypropyl methylcellulose biopolymers contained lower saturation level, solid fat content, induction period of oxidation, and firmness but a higher melting point, as compared to that made using ethylcellulose.

Topics: Biopolymers; Cellulose; Hypromellose Derivatives; Methylcellulose; Organic Chemicals

The objective was to develop eperisone HCl sustained-release pellets through extrusion spheronization technique and to determine the influence of different hydrophobic (polymeric based and wax-based) and hydrophilic (polymeric based) matrix former on the release of eperisone HCl (BCS class I drug) and on pellet sphericity. The pellet formulations consisted of different hydrophobic and hydrophilic matrix formers like HPMC K4M (10-20%) HPMC K15M (10%), EC (7cps) (10-20%), Carnauba wax (10-20%), Compritol ATO 888 (10-20%), Glyceryl monostearate (10%), lactose and microcrystalline cellulose. The initial burst release of the drug from matrix pellet formulations was effectively controlled by coating with 5% EC (ethylcellulose) dispersion. The dissolution profile and drug release kinetics of coated pellet formulations were determined at both acidic and basic pH medium. SEM (Scanning electron microscope) technique was used to determine the surface morphology and cross-section of F5 and F7 pellet formulation. The mechanism of drug release of coated formulation followed non-Fickian diffusion. FTIR spectroscopy was conducted and no drug and excipients interaction was observed. The results had shown that optimized coated formulation was F5 and F7 which effectively extend the drug release for 12 hours.

Topics: Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Development; Drug Liberation; Excipients; Fatty Acids; Glycerides; Lactose; Methylcellulose; Microscopy, Electron, Scanning; Muscle Relaxants, Central; Polymers; Propiophenones; Spectroscopy, Fourier Transform Infrared; Waxes

Topics: Animals; Cellulose; Dosage Forms; Excipients; Gastrointestinal Tract; Male; Methylcellulose; Particle Size; Pharmaceutical Preparations; Pilot Projects; Polymers; Polyvinyls; Positron Emission Tomography Computed Tomography; Printing, Three-Dimensional; Rats; Rats, Sprague-Dawley; Rodentia; Technology, Pharmaceutical

The present work was based on the development and characterization of unfolding type gastro retentive dosage form appropriate for controlled release of Cinnarizine (CNZ), a drug with narrow therapeutic window. The drug loaded polymer film of biological macromolecules, i.e., ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC K15) was folded into hard gelatin capsules. The film was folded in different patterns for characterizing their unfolding behavior. The polymeric film revealed a fast release during the first hour followed by a more gradual drug release during a 12-h period following a non-Fickian diffusion process. Tensile strength of polymeric film was optimized using different amount (0.2-0.7 ml) of polyethylene glycol (PEG 400). Various physical parameters were studied for evaluating their performance as a gastroretentive dosage form. Drug and polymers were found to be compatible as revealed by differential scanning calorimetry (DSC) study and scanning electron micrograph (SEM) study revealed uniform dispersion of CNZ in polymeric matrices. The results indicate that unfolding type gastro retentive drug delivery system holds lots of potential for drug having stability problems in alkaline pH or are which mainly absorbed in acidic pH.

Topics: Cellulose; Cinnarizine; Delayed-Action Preparations; Drug Delivery Systems; Drug Stability; Hypromellose Derivatives; Kinetics; Mechanical Phenomena; Methylcellulose; Polymers

This work focused on the control of the manufacturing process for a controlled release (CR) pellet product, within a Quality by Design (QbD) framework. The manufacturing process was Wurster coating: firstly layering active pharmaceutical ingredient (API) onto sugar pellet cores and secondly a controlled release (CR) coating. For each of these two steps, development of a Process Analytical Technology (PAT) method is discussed and also a novel application of automated microscopy as the reference method. Ultimately, PAT methods should link to product performance and the two key Critical Quality Attributes (CQAs) for this CR product are assay and release rate, linked to the API and CR coating steps respectively. In this work, the link between near infra-red (NIR) spectra and those attributes was explored by chemometrics over the course of the coating process in a pilot scale industrial environment. Correlations were built between the NIR spectra and coating weight (for API amount), CR coating thickness and dissolution performance. These correlations allow the coating process to be monitored at-line and so better control of the product performance in line with QbD requirements.

Topics: Automation, Laboratory; Cellulose; Citrates; Delayed-Action Preparations; Hypromellose Derivatives; Kinetics; Methylcellulose; Microscopy; Pharmaceutical Preparations; Quality Control; Solubility; Spectroscopy, Near-Infrared; Technology, Pharmaceutical

Garcinia mangostana Linn extract (GME) is a natural product that has received considerable attention in cancer therapy, and has the potential to reduce side effects of chemotherapeutics and improve efficacy. We formulated GME-encapsulated ethyl cellulose (GME-EC) and a polymer blend of ethyl cellulose and methyl cellulose (GME-EC/MC) nanoparticles. We achieved high drug-loading and encapsulation efficiency using a solvent-displacement method with particle sizes around 250 nm. Cellular uptake and accumulation of GME was higher for GME-encapsulated nanoparticles compared to free GME. In vitro cytotoxicity analysis showed effective anticancer activity of GME-EC and GME-EC/MC nanoparticles in HeLa cells in a dose-dependent manner. GME-EC/MC nanoparticles showed approximately twofold-higher anticancer activity compared to GME-EC nanoparticles, likely due to their enhanced bioavailability. GME-encapsulated nanoparticles primarily entered HeLa cells by clathrin-mediated endocytosis and trafficked through the endolysosomal pathway. As far as we know, this is the first report on the cellular uptake and intracellular trafficking mechanism of drug-loaded cellulose-based nanoparticles. In summary, encapsulation of GME using cellulose-derivative nanoparticles - GME-EC and GME-EC/MC nanoparticles - successfully improved the bioavailability of GME in aqueous solution, enhanced cellular uptake, and displayed effective anticancer activity.

Topics: Antineoplastic Agents; Cell Survival; Cellulose; Endocytosis; Garcinia mangostana; HeLa Cells; Humans; Intracellular Space; Methylcellulose; Plant Extracts

A promising glipizide formulation comprising compression of four-layer coated beads into tablets was prepared. The tablet offered the advantages of: a two-hour lag time before drug release, retaining sustained release characteristics and providing approximately zero-order drug release. Drug release was nearly independent of paddle speeds of 50 and 100 rpm releasing 80% over 14 h similar to the commercial glipizide osmotic pump tablet during dissolution testing while keeping the benefits of multiparticular dosage forms. The tablets contain beads with four layers: (1) the innermost layer consists of 2.5 g glipizide and 3.75 g solid ethylcellulose (Surelease®) coated onto 71.25 g of sugar beads; (2) next a hardening layer of 5 g of hypromellose; (3) the controlled release layer of 7.5 g of Surelease®:lactose at a solids ratio of 100:7 and (4) an outermost layer of 20 g of lactose:sodium starch glycolate (Explotab®) at a 2:1 ratio. Then, beads were compressed into tablets containing 11 mg of glipizide using 1500 lbs of compression pressure. The dissolution test similarity factor (f2) was above 50 for all test conditions for formulation F13 and Glucotrol® with a high of 69.9. The two Surelease® layers both aid controlling drug release, with the Surelease®-drug layer affecting drug release to a greater extent.

Topics: Cellulose; Delayed-Action Preparations; Drug Compounding; Glipizide; Hypoglycemic Agents; Hypromellose Derivatives; Lactose; Methylcellulose; Solubility; Starch; Tablets

This study aimed to develop and evaluate a novel multi-unit tablet that combined a pellet with a sustained-release coating and a tablet with a pulsatile coating for the treatment of circadian rhythm diseases. The model drug, isosorbide-5-mononitrate, was sprayed on microcrystalline cellulose (MCC)-based pellets and coated with Eudragit(®) NE30D, which served as a sustained-release layer. The coated pellets were compressed with cushion agents (a mixture of MCC PH-200/ MCC KG-802/PC-10 at a ratio of 40:40:20) at a ratio of 4:6 using a single-punch tablet machine. An isolation layer of OpadryII, swellable layer of HPMC E5, and rupturable layer of Surelease(®) were applied using a conventional pan-coating process. Central-composite design-response surface methodology was used to investigate the influence of these coatings on the square of the difference between release times over a 4 h time period. Drug release studies were carried out on formulated pellets and tablets to investigate the release behaviors, and scanning electron microscopy (SEM) was used to monitor the pellets and tablets and their cross-sectional morphology. The experimental results indicated that this system had a pulsatile dissolution profile that included a lag period of 4 h and a sustained-release time of 4 h. Compared to currently marketed preparations, this tablet may provide better treatment options for circadian rhythm diseases.

Topics: Administration, Oral; Angina Pectoris; Cardiovascular Agents; Cellulose; Chemistry, Pharmaceutical; Chronobiology Disorders; Delayed-Action Preparations; Drug Carriers; Excipients; Hypromellose Derivatives; Isosorbide Dinitrate; Kinetics; Methacrylates; Methylcellulose; Microscopy, Electron, Scanning; Polymers; Solubility; Tablets; Technology, Pharmaceutical

The present research work focused on the comparative assessment of porous versus nonporous films in order to develop a suitable buccoadhesive device for the delivery of glibenclamide. Both films were prepared by solvent casting technique using the 3(2) full factorial design, developing nine formulations (F1-F9). The films were evaluated for ex vivo mucoadhesive force, ex vivo mucoadhesion time, in vitro drug release (using a modified flow-through drug release apparatus), and ex vivo drug permeation. The mucoadhesive force, mucoadhesion time, swelling index, and tensile strength were observed to be directly proportional to the content of HPMC K4M. The optimized porous film (F4) showed an in vitro drug release of 84.47 ± 0.98%, ex vivo mucoadhesive force of 0.24 ± 0.04 N, and ex vivo mucoadhesion time of 539.11 ± 3.05 min, while the nonporous film (NF4) with the same polymer composition showed a release of 62.66 ± 0.87%, mucoadhesive force of 0.20 ± 0.05 N, and mucoadhesive time of 510 ± 2.00 min. The porous film showed significant differences for drug release and mucoadhesion time (p < 0.05) versus the nonporous film. The mechanism of drug release was observed to follow non-Fickian diffusion (0.1 < n < 0.5) for both porous and nonporous films. Ex vivo permeation studies through chicken buccal mucosa indicated improved drug permeation in porous films versus nonporous films. The present investigation established porous films to be a cost-effective buccoadhesive delivery system of glibenclamide.

Topics: Algorithms; Animals; Cellulose; Chickens; Drug Delivery Systems; Glyburide; Hydrogen-Ion Concentration; Hypoglycemic Agents; In Vitro Techniques; Kinetics; Lactose; Methylcellulose; Microscopy, Electron, Scanning; Mouth Mucosa; Porosity; Saliva; Tensile Strength; Tissue Adhesives

Curcumin is known for its anti-inflammatory, antioxidative, and anticarcinogenic properties. However, the strong lipophilic compound is not easily applicable, neither in water, nor directly in o/w formulations. So far, loading of nano or micro scaled carriers has enabled only an uptake up to 30% of curcumin.. In the present article, curcumin was successfully encapsulated into two different safe and inexpensive polymers, ethyl cellulose and methyl cellulose blended ethyl cellulose with a loading capacity of ~ 46-48%. In addition, the in vitro skin penetration of the two curcumin encapsulated particular systems, which were applied each in three different formulations, an o/w, w/o lotion, and water suspension, was investigated on porcine ear skin using Laser scanning microscopy.. It was found that in comparison to water suspensions, o/w and w/o lotions enhanced, especially the follicular penetration of the encapsulated curcumin particles into porcine skin, whereas the w/o enhanced the penetration better than the o/w lotion. Furthermore, the application of ethyl cellulose blended with methyl cellulose improved the penetration of curcumin in all formulations.. High loaded encapsulated curcumin systems, prepared from a simple and highly efficient encapsulation system can be used to transport curcumin effectively into the skin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Capsules; Cellulose; Chemistry, Pharmaceutical; Curcumin; Drug Carriers; Ear, External; Hair Follicle; Methylcellulose; Microscopy, Confocal; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Microspheres; Nanoparticles; Skin; Skin Cream; Swine; Water

The method to prepare mucosa-plates, glass slides covalently coated with mucin, is demonstrated. The use of the plate to evaluate mucoadhesion of nanocarriers made from different four polymeric materials, N-succinylchitosan (NS-chitosan), alginate (ALG), ethylcellulose (EC), and a blend of EC and methylcellulose (EC/MC), was demonstrated. While different mucoadhesion of the four carriers could be detected using mucosa-plate, the conventional viscosity measurement could not differentiate their mucin-binding ability. ALG and NS-chitosan nanospheres showed the best attachment to the mucosa-plate compared to the EC/MC and EC spheres. Capsaicin, a model hydrophobic drug, was loaded into the carriers and the ability of the different polymeric carriers to retain capsaicin at the stomach tissue was compared using an ex vivo fresh porcine stomach assay. Ability to retain capsaicin at the stomach tissue correlated well with binding affinity toward the mucosa-plate and the loading capacity of the carriers.

Topics: Adhesiveness; Alginates; Animals; Capsaicin; Cellulose; Chitosan; Drug Carriers; Gastric Mucosa; Glucuronic Acid; Hexuronic Acids; Humans; Hydrophobic and Hydrophilic Interactions; Methylcellulose; Mucins; Mucous Membrane; Nanospheres; Swine; Viscosity

Controlled release (CR) matrix tablet of Prochlorperazine maleate was developed to improve its patient compliance.. Tablet formulations F1, F2 and F3 based on different concentrations of Methocel(®) K100 LV-CR Premium, were compacted by direct compression method while tablet formulations F4, F5 and F6, based on distinct blends of Methocel(®) K100 LV-CR Premium and Ethocel(®) Standard 7FP Premium, were compressed by flow-bound dry granulation-slugging method. The prepared powder mixtures, granules and tablets were evaluated for their physicochemical performance. Bioequivalence study of the optimized test tablet versus reference-conventional Stemitil(®) tablet was conducted on rabbits, using HPLC-UV system at λ(max) 254 nm.. The test tablet, containing 28% Methocel(®) and 58% Ethocel(®) (F6) exhibited desired zero order kinetics for 24 h and was found stable at accelerated storage conditions for 6 months. In vitro drug release rate decreased as the Ethocel(®) content in the blend was increased, perhaps due to slower penetrability of water. Hydrodynamic conditions and hardness of tablets could not affect drug release kinetics. The tablet displayed significantly (p < 0.05) optimized peak drug concentration-C(max) (45 ± 3.42 vs. 64.5 ± 4.03), extended half life-t(1/2) (16.071 ± 3.97 vs. 5.257 ± 1.314 h) and bioequivalence to the reference tablet taken three times a day (1409 ± 15 ng·h/mL vs. 1346 ± 23 ng h/mL). The tablet showed strong Level A correlation (R(2) = 0.8458) between drug absorbed in vivo and drug released in vitro.. The developed tablet may be adopted by pharmaceutical industry to improve patient compliance of the Prochlorperazine maleate.

Topics: Animals; Antipsychotic Agents; Biological Availability; Cellulose; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Drug Delivery Systems; Humans; Male; Methylcellulose; Polymers; Prochlorperazine; Rabbits; Tablets; Therapeutic Equivalency

Among thymol, carvacrol, citronellal, eugenol and terpinen-4-ol, thymol showed the highest antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Thymol was then encapsulated into water dispersible submicron sized ethylcellulose/methylcellulose spheres, attaining the relatively high thymol loading level of 43.53% (weight of encapsulated thymol to weight of the thymol-loaded spheres). When tested against the same three bacterial strains, the encapsulated thymol gave comparable minimal inhibition concentration (MIC) and minimal bactericidal concentration (MBC) values to the unencapsulated compound while mostly showing lower MIC and MBC values than the conventionally used preservative, methyl-p-hydroxybenzoate (methylparaben). The use of encapsulated thymol at 0.078, 0.156 and 0.625 mg ml(-1) (0.52, 1.04 and 4.16 mmol(-1), respectively) in cosmetic lotion formulations provided total suppression of viable E. coli, S. aureus and P. aeruginosa growth (all initially seeded at 10(5) cfu ml(-1)), respectively, over the three month test period, whereas unencapsulated thymol showed effective suppression for only 2-4 weeks. Effective bacterial suppression by encapsulated thymol was also observed when used in cream and aqueous gel cosmetic formulations.

Topics: Anti-Bacterial Agents; Cellulose; Cosmetics; Escherichia coli; Excipients; Gels; Methylcellulose; Microbial Sensitivity Tests; Nanospheres; Parabens; Particle Size; Preservatives, Pharmaceutical; Pseudomonas aeruginosa; Skin Cream; Staphylococcus aureus; Thymol; Time Factors

The phytochemical curcumin possesses antioxidant activity; however, it becomes unstable after being exposed to light or heat or loses activity during storage. This is especially important when curcumin is applied to the skin within a cosmetic or pharmaceutical formulation, since sun exposure is unavoidable. This drawback can be directly addressed by encapsulation of curcumin in photo-stable nanospheres. Therefore, curcumin was encapsulated into nanoparticles consisting of ethyl cellulose and/or methyl cellulose. Nanoparticles were subjected to processing conditions commonly used in industry, for example, temperature and pressure and thus retained their morphology. Furthermore, sun exposure resulted in the protection of curcumin by nanoparticles, whereas non-encapsulated curcumin degraded completely. Determination of the radical protection factor resulted in similar antioxidant activity of encapsulated and non-encapsulated curcumin indicating that curcumin maintains its antioxidant activity. Application of lotions containing curcumin or curcumin nanoparticles to the skin and subsequent UVB-irradiation resulted in less radical formation compared to lotion application only. Moreover, radical formation was even less after nanoparticle application compared to free curcumin. Nanoencapsulation protects curcumin from photo degradation and can therefore prolong the antioxidant activity of curcumin.

Topics: Administration, Cutaneous; Animals; Antioxidants; Cellulose; Curcumin; Drug Stability; Drug Storage; Free Radical Scavengers; In Vitro Techniques; Methylcellulose; Nanoparticles; Photolysis; Pressure; Skin; Sunlight; Swine; Temperature; Time Factors; Ultraviolet Rays

Hydrophilic and hydrophobic polymer-based nicorandil (10 mg)-loaded peroral tablets were prepared using the wet granulation technique. The influence of varying amounts of hydroxypropyl methylcellulose (HPMC) (30-50 mg), ethylcellulose (2-4 mg), microcrystalline cellulose (5-20 mg) and Aerosil® (5-12 mg) in conjunction with the constant amounts (3 mg) of glidant and lubricant (magnesium stearate and talc) on the in vitro performances of the tablets (hardness, friability, weight variation, thickness uniformity, drug content, and drug release behavior) were investigated.. The objectives of this study were (i) to select a nicorandil-loaded peroral tablet that matched the in vitro dissolution profile of once-daily commercial sustained-release tablet, and (ii) to compare the in vivo sustaining/controlling efficacy of the selected peroral tablet with that of its commercial counterparts.. Because the nicorandil (10 mg)-loaded tablet prepared based on F-IX composition (50 mg HPMC, 4 mg ethylcellulose, 10 mg MCC and 3 mg glidant and lubricant) showed a release profile comparable to that of the Nikoran® OD SR tablet release profile, the tablet with this composition was considered to be the optimized/selected formulation and, therefore, was subjected to stability study and in vivo study in rabbits. Despite of the higher C(max) and AUC values obtained with the optimized tablet, there was no sign of difference between the optimized- and Nikoran® OD SR- tablets following a single-dose crossover oral administration into rabbit.. The optimized tablet could be used as an alternative to the commercial once-daily tablet.

Topics: Animals; Biological Availability; Cellulose; Delayed-Action Preparations; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; Methylcellulose; Nicorandil; Rabbits; Silicon Dioxide; Solubility; Tablets

The principle aim of this study was to design a controlled release (CR), bioadhesive formulation of miglitol (in form of pellets) which would regulate the post-prandial glucose levels via reversible inhibition of α-glucosidase enzyme as well as by modulating the glucagon-like peptide-1 (GLP-1) pathway in non-diabetic canines. A multilayered pellet formulation which was both bioadhesive (because of hydroxy propyl methyl cellulose polymer) and CR (because of the ethyl cellulose layer) was formulated. We report a novel finding that the CR formulation of miglitol (S3) induced a 2.2-fold elevation in the C(max) as well as the overall AUC(0-24) of GLP-1 values in comparison to the non-CR (immediate release (IR) formulation). The S3 formulation also resulted in better, steady, and prolonged control of glucose levels over a time period of 7 h in comparison to the IR formulation possibly due to combination of both, prolonged inhibition of the α-glucosidase enzyme and enhanced plasma GLP-1 levels. The S3 formulation was stable with no changes in the dissolution profiles at both of the stability conditions tested, 25°C/60% RH and 40°C/75% RH. Aqueous polymeric coating of the pellets (in contrast to coating using organic solvents) resulted morphologically in a uniform polymeric film and also releases profiles with lower burst effect. Curing played a significant role in determining release profile of the pellets, prepared by aqueous polymeric coating method.

Topics: 1-Deoxynojirimycin; alpha-Glucosidases; Animals; Biological Availability; Blood Glucose; Cellulose; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dogs; Drug Implants; Enteroendocrine Cells; Glucagon-Like Peptide 1; Glycoside Hydrolase Inhibitors; Intestine, Small; Male; Methylcellulose; Polymers; Postprandial Period; Rats; Rats, Sprague-Dawley

Dry powder coating is a technique to coat substrates without the use of organic solvent or water. The polymer powder is directly applied to the cores to be coated. Liquid additives are often used to lower the glass transition temperature of the polymer and to enhance the adhesion of the powder to the cores. This leads to an increase in coating efficiency of the process. The impact of various liquid additives and their properties like spreading behavior, viscosity and plasticizing activity were investigated with respect to their influence on the coating efficiency of the process. Ethylcellulose and hydroxypropyl methylcellulose acetate succinate were used as coating polymers. Spreading behavior of the liquid additive on the polymer was the most influencing parameter and could be successfully predicted with contact angle measurements on polymer films. Calculations of works of adhesion and spreading coefficients also revealed to be promising predictive techniques for choosing suitable additives to improve process efficiency. Isopropyl myristate showed the best spreading behavior resulting in the highest coating efficiency. Based on these results, a formulation for ethylcellulose containing isopropyl myristate was developed and film formation was examined using dissolution testing and imaging techniques to evaluate the optimum curing conditions.

Topics: Cellulose; Drug Compounding; Excipients; Methylcellulose; Polymers; Powders; Pressure; Solubility; Surface Tension; Transition Temperature; Viscosity

The aim was to design a pH-sensitive pulsatile drug delivery system that allows for an on-off pulsed release of a drug using polyacrylic acid (PAA) blended with ethyl cellulose (EC) in different ratios. PAA, a polyelectrolyte polymer, exhibits a highly coiled conformation at low pH but a highly extended structure at high pH. Fumaric acid, which is an internal acidifying agent, was incorporated into the hydroxypropyl methylcellulose-based core tablets to create an acidic microenvironmental pH (pH(M)). The concentration of fumaric acid inside the core tablet and the ratio of PAA/EC in the coating layer were very crucial in modulating drug release behaviors. When the fumaric acid was retained in the core tablet, it gave a more acidic pH(M), so that the PAA was kept in a highly coiled state in the coated film, which hindered drug release ("off" release pattern). Interestingly, the release profiles of the drug and fumaric acid from coated tablets showed the on-off pulsed pattern upon dissolution. Imaging analyses using scanning electron microscopy, near-infrared imaging, confocal laser scanning microscopy, and Fourier transform infrared spectroscopy confirmed this on-off release behavior of the drug and fumaric acid from coated tablets.

Topics: Acrylic Resins; Bronchodilator Agents; Cellulose; Delayed-Action Preparations; Drug Compounding; Excipients; Fumarates; Hydrogen-Ion Concentration; Hypromellose Derivatives; Methylcellulose; Microscopy, Confocal; Polymers; Solubility; Spectroscopy, Fourier Transform Infrared; Spectroscopy, Near-Infrared; Tablets; Terbutaline

The objective of this study was to develop sustained release (SR) matrix tablets of metoprolol succinate (MS), by using different polymer combinations and fillers, to optimize by response surface methodology and to evaluate biopharmaceutical parameters of the optimized product. Matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC); and lactose and dibasic calcium phosphate dihydrate (DCP) as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was subjected to further study like scanning electron microscopy, swelling study and in vivo study in rabbit model. Both in vitro and in vivo study revealed that combining of HPMC K100M (21.95%) with EC (8.85%), and use of DCP as filler sustained the action up to 12 h. The in vivo study of new SR tablets showed significant improvement in the oral bioavailability of MS in rabbits after a single oral dose of 25 mg. The delayed T(max) and lower C(max) indicated a slow and SR of MS from the optimized matrix tablets in comparison with the immediate release dosage form. The developed SR (MS) tablet of improved efficacy can perform therapeutically better than conventional tablet.

Topics: Administration, Oral; Adrenergic beta-1 Receptor Antagonists; Animals; Biological Availability; Cellulose; Delayed-Action Preparations; Drug Delivery Systems; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; Methylcellulose; Metoprolol; Models, Animal; Rabbits

The objective of the study was to formulate and evaluate controlled release polymeric tablets of Diclofenac Potassium for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with different types and grades of Ethyl Cellulose Ether derivatives in several drug-to-polymer ratios (D:P) were compressed into tablets using the direct compression method. In vitro drug release studies were performed in phosphate buffer (pH 7.4) as dissolution medium by using USP Method-1 (Rotating Basket Method). Similarity factor f2 and dissimilarity factor f1 were applied for checking the similarities and dissimilarities of the release profiles of different formulations. For the determination of the release mechanism and drug release kinetics various mathematical/kinetic models were employed. It was found that all of the Ethocel polymers could significantly slow down the drug release rate with Ethocel FP polymers being the most efficient, especially at D:P ratios of 10:03 which lead towards the achievement of zero or near zero order release kinetics.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Carboxymethylcellulose Sodium; Cellulose; Diclofenac; Excipients; Hypromellose Derivatives; Methylcellulose; Solubility; Tablets

Controlled-release (CR) matrix tablet of 4 mg risperidone was developed using flow bound dry granulation-slugging method to improve its safety profile and compliance. Model formulations F1, F2, and F3, consisting of distinct blends of Methocel® K100 LV-CR and Ethocel® standard 7FP premium, were slugged. Each batch of granules (250-1,000 μm), obtained by crushing the slugs, was divided into three portions after lubrication and then compressed to 9-, 12-, and 15-kg hard tablets. In vitro drug release studies were carried out in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using a paddle dissolution apparatus run at 50 rpm. The CR test tablet, containing 30% Methocel® and 60% Ethocel® (F3) with 12-kg hardness, exhibited pH-independent zero-order release kinetics for 24 h. The drug release rate was inversely proportional to the content of Ethocel®, while the gel layer formed of Methocel® helped in maintaining the integrity of the matrix. Changes in the hardness of tablet did not affect the release kinetics. The tablets were reproducible and stable for 6 months at 40 ± 2°C/75 ± 5% relative humidity. Risperidone and its active metabolite, 9-hydroxyrisperidone, present in the pooled rabbit's serum, were analyzed with HPLC-UV at λ(max) 280 nm. The CR test tablet exhibited bioequivalence to reference conventional tablet in addition to the significantly (p < 0.05) optimized peak concentration, C(max), and extended peak time, T (max), of the active moiety. There was a good association between drug absorption in vivo and drug release in vitro (R(2) = 0.7293). The successfully developed CR test tablet may be used for better therapeutic outcomes of risperidone.

Topics: Animals; Biological Availability; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Interactions; Female; Male; Methylcellulose; Polymers; Rabbits; Risperidone; Tablets, Enteric-Coated

The basic objective of this study is to develop the Flurbiprofen sodium soluble ocusert to increase patient compliance by improving local delivery of the drug.. Three different polymers were used in combination to prepare the rate controlling membrane. The drug reservoir was prepared by using hydroxy propyl methyl cellulose. Ocuserts were evaluated for their physicochemical parameters. The optimized formulations were further evaluated for accelerated stability studies, eye irritancy tests, and for in vivo drug release studies.. Ocuserts were found stable at room temperature and showed a strong positive correlation between in vitro and in vivo drug release.. An appropriate combination of hydrophilic and hydrophobic polymers provides better control of drug delivery.

Topics: Acrylic Resins; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Drug Carriers; Drug Delivery Systems; Drug Design; Drug Evaluation; Female; Flurbiprofen; Hydrogen-Ion Concentration; Hypromellose Derivatives; Male; Methylcellulose; Patient Compliance; Rabbits; Temperature

Being controlled release dosage forms, tablets allow an improved absorption and release profiles of Ofloxacin. The fact that drugs with fine particles size can be compressed well after wetting, so in our research studies Ofloxacin controlled release matrix tablets were prepared by wet granulation technique. In order to investigate the potential of Ethyl cellulose ether derivatives as a matrix material, Ofloxacin formulations with different types and grades of Ethocel were prepared at several drug-to-polymer ratios. The method adopted for in vitro drug release studies was USP Method-1 (rotating Basket Method) by Pharma test dissolution apparatus using phosphate buffer 7.4 pH as a dissolution medium. Various Kinetic models were employed to the formulations for the purpose of determination of release mechanism. A comparative study was performed between the tested Ofloxacin-Ethocel formulations and a standard reference obtained from the local market. F1 dissimilarity factor and f2 similarity factor were applied to the formulations for the checking of dissimilarities and similarities between the tested formulations and reference standard.

Topics: Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Excipients; In Vitro Techniques; Methylcellulose; Models, Statistical; Ofloxacin; Reference Standards; Solubility; Tablets

Existing encapsulated organic phase change materials (PCM) usually contain a shell material that possesses a poor heat storage capacity and so results in a lowered latent heat storage density of the encapsulated PCM compared to unencapsulated PCM. Here, we demonstrate the use of a novel microencapsulation process to encapsulate n-eicosane (C20) into a 2:1 (w/w) ratio blend of ethyl cellulose (EC):methyl cellulose (MC) to give C20-loaded EC/MC microspheres with an increased heat storage capacity compared to the unencapsulated C20. Up to a 29 and 24% increase in the absolute enthalpy value during crystallization and melting were observed for the encap-C20/EC/MC microparticles with a 9% (w/w) EC/MC polymer content. The mechanism that leads to the increased latent heat storage capacity is discussed. The blending of the water-dispersible C20-loaded EC/MC microspheres into natural rubber latex showed excellent compatibility, and the obtained rubber composite showed not only an obvious thermoregulation property but also an improved mechanical property.

Topics: Alkanes; Calorimetry, Differential Scanning; Cellulose; Crystallization; Methylcellulose; Microspheres; Phase Transition; Rubber

The bioavailability of therapeutic agents from eye drops is usually limited due to corneal barrier functions and effective eye protective mechanisms. Therefore, the current study aims to enhance ocular bioavailability of brimonidine, a potent antiglaucoma drug, through the preparation of ocular inserts. Solvent casting technique was employed to prepare the inserts using polyvinylpyrrolidone K-90 (PVP K-90) as film-forming polymer blended with different viscosity grades of bioadhesive polymers namely hydroxypropyl methycellulose, carbopol, sodium alginate, and chitosan. The prepared ocular inserts were evaluated for various physicochemical parameters, swelling behavior, and in vitro release patterns. Sodium alginate-based ocular inserts revealed the most sustainment in drug release (99% at 6 h), so it was selected for further modifications via coating it, on one side or dual sides, using hydrophobic film composed of either ethylcellulose or Eudragit RSPO. The obtained in vitro release results for the modified ocular inserts revealed that ethylcellulose is superior to Eudragit RSPO in terms of brimonidine release sustainment effect. Ocular inserts composed of 7% PVP K-90, 1.5% low molecular weight sodium alginate with or without ethylcellulose coat were able to sustain the in vitro release of brimonidine. Their therapeutic efficacy regarding intraocular pressure (IOP) lowering effect when inserted in albino rabbits eyes showed superior sustainment effect compared with that of brimonidine solution. Furthermore, due to both the mucoadhesive property and the drug sustainment effect, the one-side-coated ocular insert showed more IOP lowering effect compared with that of its non-coated or dual-side-coated counterpart.

Topics: Absorbable Implants; Acrylic Resins; Administration, Ophthalmic; Adrenergic alpha-2 Receptor Agonists; Alginates; Animals; Brimonidine Tartrate; Calorimetry, Differential Scanning; Cellulose; Chemistry, Pharmaceutical; Chitosan; Delayed-Action Preparations; Disease Models, Animal; Drug Carriers; Drug Compounding; Glaucoma; Glucuronic Acid; Hexuronic Acids; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; Intraocular Pressure; Kinetics; Methylcellulose; Ophthalmic Solutions; Polymers; Polymethacrylic Acids; Polyvinyls; Povidone; Quinoxalines; Rabbits; Solubility; Spectroscopy, Fourier Transform Infrared; Technology, Pharmaceutical; X-Ray Diffraction

The present work reports the study of different controlled release formulations of ketoprofen, which is a non-steroidal anti-inflammatory drug (NSAID) and like other NSAIDs requires large and frequent daily doses, resulting in severe side effects and non-compliance. To avoid these problems, controlled release matrices were developed using different grades of ethylcellulose polymer with a drug-polymer ratio of 10:3 by the direct compression method. The effect on drug release of partial replacement of lactose by different co-excipients, HPMC K100 M, starch and CMC, was also studied. The tablets were tested for their drug content, weight variation, friability, hardness, thickness and diameter, all these physical properties being within the USP range. The release profile of all formulations containing polymer and co-excipients was compared with a formulation developed without polymer and co-excipients. After a 24-hour release study, it was concluded that formulations containing different grades of ethylcellulose polymer showed prolonged release for 6-18 hours, but the formulation containing the polymer Ethocel standard FP 7 Premium without co-excipient showed controlled release for 24 hours. DSC and FT-IR studies were performed to investigate any incompatibility between drug, polymer and co-excipient but no interaction was found. Different kinetic models were used, such as first order equation, zero order equation, Higuachi equation, Hixon Crowel's equation and Korsmeyer-Peppas to study the release mechanism. The formulations containing co-excipients showed an enhanced release rate.

Topics: Algorithms; Anti-Inflammatory Agents, Non-Steroidal; Calorimetry, Differential Scanning; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Excipients; Hypromellose Derivatives; Indicators and Reagents; Ketoprofen; Kinetics; Methylcellulose; Solubility; Spectroscopy, Fourier Transform Infrared; Starch; Tablets; Temperature

The six fragrances, camphor, citronellal, eucalyptol, limonene, menthol and 4-tert-butylcyclohexyl acetate, which represent different chemical functionalities, were encapsulated with a polymer-blend of ethylcellulose (EC), hydroxypropyl methylcellulose (HPMC) and poly(vinyl alcohol) (PV(OH)) using solvent displacement (ethanol displaced by water). The process gave >or=40% fragrance loading capacity with >or=80% encapsulation efficiency at the fragrance to polymer weight ratio of 1:1 and at initial polymer concentrations of 2000-16,000 ppm and the obtained fragrance-encapsulated spheres showed hydrodynamic diameters of less than 450 nm. The release profile of the encapsulated fragrances, evaluated by both thermal gravimetric and electronic nose techniques, indicated different release characteristics amongst the six encapsulated fragrances. Limonene showed the fastest release with essentially no retention by the nanoparticles, while eucalyptol and menthol showed the slowest release.

Topics: Cellulose; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Hypromellose Derivatives; Methylcellulose; Nanoparticles; Oils, Volatile; Particle Size; Perfume; Polymers; Solvents; Surface Properties

Controlled-release (CR) tablet formulation of olanzapine was developed using a binary mixture of Methocel® K100 LV-CR and Ethocel® standard 7FP premium by the dry granulation slugging method. Drug release kinetics of CR tablet formulations F1, F2, and F3, each one suitably compressed for 9-, 12-, and 15-kg hardness, were determined in a dissolution media of 0.1 N HCl (pH 1.5) and phosphate buffer (pH 6.8) using type II dissolution apparatus with paddles run at 50 rpm. Ethocel® was found to be distinctly controlling drug release, whereas the hardness of tablets and pH of the dissolution media did not significantly affect release kinetics. The CR test tablets containing 30% Methocel® and 60% Ethocel® (F3) with 12-kg hardness exhibited pH-independent zero-order release kinetics for 24 h. In vivo performance of the CR test tablet and conventional reference tablet were determined in rabbit serum using high-performance liquid chromatography coupled with electrochemical detector. Bioavailability parameters including C(max), T(max), and AUC(0-48 h) of both tablets were compared. The CR test tablets produced optimized C(max) and extended T(max) (P < 0.05). A good correlation of drug absorption in vivo and drug release in vitro (R(2) = 0.9082) was observed. Relative bioavailability of the test tablet was calculated as 94%. The manufacturing process employed was reproducible and the CR test tablets were stable for 6 months at 40 ± 2°C/75 ± 5% relative humidity. It was concluded that the CR test tablet formulation successfully developed may improve tolerability and patient adherence by reducing adverse effects.

Topics: Animals; Benzodiazepines; Biological Availability; Cellulose; Delayed-Action Preparations; Diffusion; Emulsions; Female; Male; Methylcellulose; Olanzapine; Rabbits; Tablets

To develop pulsatile release pellets using tanshinone II as model drug and evaluate their properties in vitro.. The tanshinone II pusatile release pellets with rupturable coatings were prepared by fluid bed. Hydroxy propyl methyl cellulose (HPMC), low-substituted hydroxy propyl cellulose (L-HPC)/HPMC, and HPMC/Sureleae were used as swelling agents respectively, and aqueous ethylcellulose dispersion Surelease as the material of controlled layer. Dissolution experiments were employed to evaluate the effects of different swelling agents and weight gain of each coating layer. Cross-sections of pellets with different swelling agents were observed by scanning electron microscope (SEM). The release profiles of tanshinone II from the coated pellets were fitted into various mathematic models.. Pellets with HPMC or L-HPC/HPMC as swelling agents could not present a significant release lag time. However, the pellets with the mixture of HPMC and Surelease as swelling agents could. As the ratio of Surelease increased in swelling layer, the lag time could be extended. As to the controlled layer, the thicker the controlled layer, the longer the lag time could be. When the controlled layer was coated by 30%-40% weight gains, 3-5 h lag time was realized. The fitted model suggested that first order equation could explain the drug release from tanshinone II pulsatile release pellets.. Using HPMC/Surelease mixture as swelling agents, and Surelease as the material of controlled layer, tanshinone II pulsatile release pellets with 3-5 h lag time were successfully prepared.

Topics: Abietanes; Administration, Oral; Cellulose; Delayed-Action Preparations; Drug Design; Drugs, Chinese Herbal; Lactose; Methylcellulose; Quality Control; Tablets

Ranolazine hydrochloride sustained-release tablet (RH-ST) was prepared and its release behavior in vitro was studied. The pharmacokinetic characteristics and bioavailability in six Beagle dogs after oral administration of RH-ST and ranolazine hydrochloride common tablets (RH-CT) as reference were compared. Three kinds of matrix, hydroxypropylmethylcellulose (HPMC K4M), ethylcellulose (EC 100cp) and acrylic resins (Eudragit RL100) were selected as functional excipients to keep ranolazine hydrochloride (RH) release for 12 hours. Through orthogonal designs, the polymers were quantified and the optimized cumulative release profile was obtained. The single oral dose of RH-ST 500 mg and RH-CT 333.3 mg was given to six dogs using a two way crossover design. Plasma levels were determined by LC-MS and the absorption fractions were calculated according to Loo-Riegelman formula. The steady-state concentration of RH in plasma of six dogs and its pharmacokinetics behaviors after continuous oral administration of RH-ST and RH-CT at different time intervals were studied by LC-MS. The steady-state pharmacokinetic parameters were computed by software program BAPP2.0. With the increase of the amount of the matrix, the drug release was decreased. The most important factor influencing drug release is the quantity of HPMC K4M. Drug release within the period (from 0 h to 12 h) fitted well into Higuchi model. The correlation coefficient (r) between the dissolution in vitro in release media of the distilled water and the absorptin fraction in vivo was 0.9550. To compare with RH-CT, RH-ST in vivo has a steady and slow release behavior, Tmax was obviously delayed (3.00 +/- 0.50) h and the relative bioavailability was over 80 percentage. The combined use of multiple polymers can decrease the tablet weight effectively, and the drug release rate can be decreased both in vitro and in vivo.

Topics: Acetanilides; Acrylic Resins; Administration, Oral; Animals; Area Under Curve; Biological Availability; Cellulose; Cross-Over Studies; Delayed-Action Preparations; Dogs; Excipients; Female; Hypromellose Derivatives; Male; Methylcellulose; Piperazines; Ranolazine; Tablets

The aim of this study was to develop sustained-release matrix tablets by means of injection moulding and to evaluate the influence of process temperature, matrix composition (EC and HPMC concentration) and viscosity grade of ethylcellulose (EC) and hydroxypropylmethylcellulose (HPMC) on processability and drug release. The drug release data were analyzed to get insight in the release kinetics and mechanism. Formulations containing metoprolol tartrate (30%, model drug), EC with dibutyl sebacate (matrix former and plasticizer) and hydrophilic polymer HPMC were extruded and subsequently injection moulded into tablets (375 mg, 10 mm diameter, convex-shaped) at temperatures ranging from 110 to 140 degrees C. Tablets containing 30% metoprolol and 70% ethylcellulose (EC 4mPa s) showed an incomplete drug release within 24 h (<50%). Increasing production temperatures resulted in a lower drug release rate. Substituting part of the EC fraction by HPMC (HPMC/EC-ratio: 20/50 and 35/35) resulted in faster and constant drug release rates. Formulations containing 50% HPMC had a complete and first-order drug release profile with drug release controlled via the combination of diffusion and swelling/erosion. Faster drug release rates were observed for higher viscosity grades of EC (Mw>20 mPa s) and HPMC (4000 and 10,000 mPa s). Tablet porosity was low (<4%). Differential scanning calorimetry (DSC) and X-ray powder diffraction studies (X-RD) showed that solid dispersions were formed during processing. Using thermogravimetrical analysis (TGA) and gel-permeation chromatography no degradation of drug and matrix polymer was observed. The surface morphology was investigated with the aid of scanning electron microscopy (SEM) showing an influence of the process temperature. Raman spectroscopy demonstrated that the drug is distributed in the entire matrix, however, some drug clusters were identified.

Topics: Calorimetry, Differential Scanning; Cellulose; Delayed-Action Preparations; Dicarboxylic Acids; Excipients; Hypromellose Derivatives; Methylcellulose; Metoprolol; Plasticizers; Porosity; Spectrum Analysis, Raman; Tablets; Technology, Pharmaceutical; Temperature; Viscosity; X-Ray Diffraction

The purpose of this research was to develop a matrix-type transdermal therapeutic system containing herbal drug, curcumin (CUR), with different ratios of hydrophilic (hydroxyl propyl methyl cellulose K4M [HPMC K4M]) and hydrophobic (ethyl cellulose [EC]) polymeric systems by the solvent evaporation technique. Different concentrations of oleic acid (OA) were used to enhance the transdermal permeation of CUR. The physicochemical compatibility of the drug and the polymers was also studied by differential scanning calorimetry (DSC) and infrared (IR) spectroscopy. The results suggested no physicochemical incompatibility between the drug and the polymers. Formulated transdermal films were physically evaluated with regard to drug content, tensile strength, folding endurance, thickness, and weight variation. All prepared formulations indicated good physical stability. In vitro permeation studies of formulations were performed by using Franz diffusion cells. The results followed Higuchi kinetics, and the mechanism of release was diffusion-mediated. Formulation prepared with hydrophilic polymer containing permeation enhancer showed best in vitro skin permeation through rat skin as compared with all other formulations. This formulation demonstrated good anti-inflammatory activity against carrageenan-induced oedema in Wistar albino rats similar to standard formulation.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cellulose; Curcumin; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Delivery Systems; Drug Design; Drug Evaluation, Preclinical; Drug Incompatibility; Drug Stability; Edema; Excipients; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; In Vitro Techniques; Kinetics; Methylcellulose; Permeability; Pharmaceutical Vehicles; Rats; Rats, Wistar; Skin; Skin Absorption; Tensile Strength

Novel doughnut-shaped multi-layered drug delivery devices (DDDs) were developed with local variations of the drug and release-retardant material for providing linear release profiles. Based on computer-aided design models, different DDDs containing acetaminophen as a model drug, hydroxypropyl methylcellulose as matrix and ethyl cellulose (EC) as a release-retardant material were prepared automatically using a three-dimensional printing (3DP) system. In vitro dissolution assays demonstrated that all the 3DP DDDs had with different diameters, heights, concentrations of EC and central hole diameters were able to give linear release profiles. Morphological and erosion studies showed that acetaminophen was released through a simultaneous surface erosion process involving the outer peripheries and inner apertures. The barrier layers on both bases of DDDs had good adhesion strength with the drug-contained regions and offered consistent release retardation for the whole duration of the dissolution process. The release time periods of the DDDs were dependent on the annular thicknesses or the passes of binder solution containing a release-retardant material. The dosage of the DDD can be adjusted independently by changing the heights of the DDDs. Thus, 3DP is capable of offering novel strategies for developing DDDs with complex design features for desired drug release profiles.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Cellulose; Chemistry, Pharmaceutical; Computer-Aided Design; Drug Compounding; Drug Delivery Systems; Excipients; Hypromellose Derivatives; Methylcellulose; Microscopy, Electron, Scanning; Pharmaceutical Preparations; Solubility; Surface Properties; Tablets; Technology, Pharmaceutical

Nifedipine release from coated commercially available immediate release soft elastic gelatin capsules was investigated. Capsules were spray coated using two different polymeric combinations, ethylcellulose and hydroxypropylmethylcellulose or pectin, at different coating loads. In vitro drug release studies were conducted in three different dissolution media: with gastric pretreatment, without gastric pretreatment, and in water to investigate the pH effect on nifedipine release. Convolution of in vitro dissolution data for selected formulations and commercially available sustained release nifedipine formulations showed that the tested formulations provided release profiles of nifedipine that are very promising in terms of desirable sustained release formulations.

Topics: Calcium Channel Blockers; Capsules; Cellulose; Delayed-Action Preparations; Excipients; Gelatin; Hydrogen-Ion Concentration; Hypromellose Derivatives; Methylcellulose; Nifedipine; Pectins; Polymers; Solubility

The present study was designed to assess and compare with a range of surfactant-coated, nimesulide-free, and nimesulide-loaded ethylcellulose/methylcellulose (EC/MC) nanoparticles that were prepared by varying drug concentration (ED/MD), polymer concentration (EP/MP), and surfactant concentration (ES/MS). EC/MC nanoparticles prepared by desolvation method produced discrete particles and they were characterized by SEM, AFM, and FTIR studies. The particles mean size diameter (nm) ranged from 244 to 1056 nm and 1065 to 1710 nm for EC and MC nanoparticles, respectively. Studies on drug: polymer ratio showed a linear relationship between drug concentration and percentage of loading in nanoparticles. The encapsulation efficiency decreased with the increase of nimesulide concentration with respect to polymer concentration. Encapsulation efficiency of drug-loaded nanoparticles was varied between 32.8% and 64.9%. The in vitro release of drug-loaded nanoparticles was found to be a first order. This was significantly increased in EC nanoparticles (95.50%) in comparison with MC nanoparticles (95.12%) after 12 h in 24 h long study. Nimesulide release from EC nanoparticles was much slower at slightly alkaline pH 7.4. The in vitro hemolysis tests of nanoparticles were carried out to ascertain the hemocompatibility and shown to be insignificant for EC nanoparticles. In comparison, ES4 from EC formulations with nimesulide was found to be promising with slow and sustained drug release.

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Drug Carriers; Hemolysis; Humans; Methylcellulose; Microscopy, Atomic Force; Nanoparticles; Particle Size; Spectroscopy, Fourier Transform Infrared; Sulfonamides

Present work conceptualizes a specific technology, based on combining floating and pulsatile principles to develop drug delivery system, intended for chronotherapy in nocturnal acid breakthrough. This approach will be achieved by using a programmed delivery of ranitidine hydrochloride from a floating tablet with time-lagged coating. In this study, investigation of the functionality of the outer polymer coating to predict lag time and drug release was statistically analyzed using the response surface methodology (RSM). RSM was employed for designing of the experiment, generation of mathematical models and optimization study. The chosen independent variables, i.e. percentage weight ratios of ethyl cellulose to hydroxypropyl methyl cellulose in the coating formulation and coating level (% weight gain) were optimized with a 3(2) full factorial design. Lag time prior to drug release and cumulative percentage drug release in 7h were selected as responses. Results revealed that both, the coating composition and coating level, are significant factors affecting drug release profile. A second-order polynomial equation fitted to the data was used to predict the responses in the optimal region. The optimized formulation prepared according to computer-determined levels provided a release profile, which was close to the predicted values. The proposed mathematical model is found to be robust and accurate for optimization of time-lagged coating formulations for programmable pulsatile release of ranitidine hydrochloride, consistent with the demands of nocturnal acid breakthrough.

Topics: Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Delivery Systems; Excipients; Gastric Acid; Histamine H2 Antagonists; Hypromellose Derivatives; Kinetics; Methylcellulose; Models, Statistical; Ranitidine; Regression Analysis; Solubility; Tablets, Enteric-Coated

Bilayered tablets of Divalproex sodium for once-a-day administration were prepared using a hydrophilic and hydrophobic polymer as release retarding agents. This technology was found to be more effective than a simple matrix tablet with a mixture of the above polymers in order to retard the drug release for a period of 24 h. The drug release profile was strongly dependent on the presence of wicking agent, pathlength of hydrophobic layer, and hardness of tablet. f(1) value of 6.92 and f(2) value of 76.72 indicated similarity between the release profiles of batch BT3 and reference tablet (Depakote((R)) ER) with the target release of over 55% within 12 h and over 85% within 18 h. Mathematical modeling using Korsmeyer-Peppas equation indicated that the release followed a combination of diffusion and erosion mechanism.

Topics: Biological Availability; Cellulose; Delayed-Action Preparations; Excipients; Fatty Alcohols; Hypromellose Derivatives; Kinetics; Methylcellulose; Models, Biological; Silicon Dioxide; Starch; Stearic Acids; Tablets; Valproic Acid

The purpose of this research work was to develop venlafaxine hydrochloride-coated and layered matrix tablets using hypromellose adopting wet granulation technique. The granules and the tablets were characterized. The monolithic tablets were coated with different ratios of ethyl cellulose and hypromellose. The in vitro dissolution study was performed in distilled water. In the layered tablets, the middle layer containing drug was covered with barrier layers containing high viscosity grade hypromellose. Simplex lattice design was used for formulating the layered tablets. The dissolution study of the optimized batches and a reference product was carried out in 0.1 N HCl, phosphate buffer and hydroalcoholic solution. Burst drug release was exhibited by the uncoated tablets, probably due to high aqueous solubility of venlafaxine HCl. The coated tablets showed sustained drug release without burst effect. The drug release was best explained by Weibull model. A unified Weibull equation was evolved to express drug release from the coated tablets. The layered tablets also exhibited sustained release without burst effect due to effective area reduction. The optimized batches showed identical drug release in 0.1 N HCl, phosphate buffer and 10% v/v aqueous alcohol. Layered tablets may well be adopted by the industry due to the possibility of achieving a high production rate.

Topics: Algorithms; Antidepressive Agents, Second-Generation; Biological Availability; Cellulose; Chemistry, Pharmaceutical; Cyclohexanols; Delayed-Action Preparations; Drug Stability; Ethanol; Excipients; Hypromellose Derivatives; Lactose; Methylcellulose; Models, Chemical; Models, Statistical; Stearic Acids; Tablets, Enteric-Coated; Venlafaxine Hydrochloride; Water

Various methods are available to formulate water soluble drugs into sustained release dosage forms by retarding the dissolution rate. One of the methods used to control drug release and thereby prolong therapeutic activity is to use hydrophilic and lipophilic polymers. In this study, the effects of various polymers such as hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC) and sodium carboxymethylcellulose (CMC) and surfactants (sodium lauryl sulphate, cetyltrimethylammonium bromide and Arlacel 60) on the release rate of captopril were investigated. The results showed that an increase in the amount of HPMC K15M resulted in reduction of the release rate of captopril from these matrices. When HPMC was partly replaced by NaCMC (the ratio of HPMC/NaCMC was 5:1), the release rate of the drug significantly decreased. However, there was no significant difference in release rate of captopril from matrices produced with ratios of 5:1 and 2:1 of HPMC/NaCMC. The presence of lactose in matrices containing HPMC and NaCMC increased the release rate of captopril. It was interesting to note that although partial replacement of HPMC by EC reduced the release rate of the drug (ratio of HPMC/EC 2:1), the release rate was increased when the ratio of HPMC/EC was reduced to 1:1. The effects of various surfactants on the release rate of captopril from HPMC/EC (1:1) matrices were also investigated. The results showed that the surfactants did not significantly change the release rate of the drug. Release data were examined kinetically and the ideal kinetic models were estimated for the drug release. The kinetic analysis of drug release data from various formulations showed that incorporation of surfactants in HPMC/EC matrices did not produce a zero-order release pattern.

Topics: Captopril; Carboxymethylcellulose Sodium; Cellulose; Cetrimonium; Cetrimonium Compounds; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Hypromellose Derivatives; Kinetics; Lactose; Methylcellulose; Models, Chemical; Polymers; Sodium Dodecyl Sulfate; Solubility; Surface-Active Agents; Technology, Pharmaceutical

This work was aimed at evaluating the effect of a pharmaceutical cationic exchange resin (Amberlite IRP-69) on the properties of controlled release matrices using Methocel K4M (HPMC) or Ethocel 7cP (EC) as matrix formers. Diphenhydramine hydrochloride (DPH), which was cationic and water soluble, was chosen as a model drug. HPMC- and EC-based matrices with varying amounts (0-40%w/w) of resin incorporation were prepared by a direct compression. Matrix properties including diameter, thickness, hardness, friability, surface morphology and drug release were evaluated. The obtained matrices were comparable in diameter and thickness regardless of the amount of resin incorporation. Increasing the incorporated resin decreased the hardness of HPMC- and EC-based matrices, correlating with the degree of rupturing on the matrix surfaces. The friability of HPMC-based matrices increased with increasing the incorporated resin, corresponding to their decreased hardness. In contrast, the EC-based matrices showed no significant change in friability in spite of decreasing hardness. The incorporated resin differently influenced DPH release from HPMC- and EC-based matrices in deionized water. The resin further retarded DPH release from HPMC-based matrices due to the gelling property of HPMC and the ion exchange property of the resin. In contrast, the release from EC-based matrices initially increased because of the disintegrating property of the resin, but thereafter declined due to the complex formation between released drug and dispersed resin via the ion exchange process. The release in ionic solutions was also described. In conclusion, the incorporated resin could alter the release and physical properties of matrices.

Topics: Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diphenhydramine; Ion Exchange Resins; Methylcellulose

We prepared the isosorbide-5-mononitrate pulsatile controlled-release pellets (PCRP) and studied the influencing factors in vitro. The isosorbide-5-mononitrate (5-ISMN) pellets prepared by extrusion-spheronization technology were coated with swelling material as the inner coating swelling layer, and with ethylcellulose aqueous dispersion as the outer coating controlled layer. The influences of the coating materials of the swelling layer, the coating levels of the swelling layer and controlled layer,and the pH values of the media on the release of 5-ISMN from PCRP were investigated. The drug release from the pellets was pulsatile. The ISMN-5-PCRP, with a lag time of 5 h and more than 80% released within the following 1.5 h,were prepared by using the low-substituted hydroxypropyl cellulose as the inner swelling layer with 15% (weight) in coating thickness, and the ethylcellulose aqueous dispersion as the outer controlling layer with 13% (weight) in coating thickness.

Topics: Capsules; Cellulose; Delayed-Action Preparations; Drug Carriers; Hypromellose Derivatives; Isosorbide Dinitrate; Methylcellulose

Captopril granules of controlled release with different polymers as ethylcellulose, ethyl/methylcellulose, and immediate release with polyvinylpyrrolidone (PVP) were developed by fluid bed dryer technique. The formulations were analyzed by scanning electron microscopy, X-ray powder diffraction, and dissolution profiles. To compare the formulations an in vivo setting rat blood pressure assay was performed, using angiotensin I as a vasoconstrictor agent. The scanning electron microscopy of granules showed differences in morphology, and X-ray powder diffraction technique presented some modification in crystalline structure of captopril in granules coated with PVP and ethyl/methylcellulose. The dissolution profile of granules coated with ethylcellulose showed a median time release of 4 hr whereas for granules coated with ethyl/methylcellulose, this time was 3.5 hr. The blockage of angiotensin I-induced hypertensive effect lasted 8 hr in granules coated with PVP and of more than 12 hr in the granules coated with ethylcellulose and ethyl/methylcellulose.

Topics: Administration, Oral; Angiotensin I; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Captopril; Cellulose; Chemistry, Pharmaceutical; Crystallography, X-Ray; Delayed-Action Preparations; Disease Models, Animal; Drug Compounding; Female; Hypertension; Kinetics; Methylcellulose; Microscopy, Electron, Scanning; Models, Chemical; Povidone; Powder Diffraction; Powders; Rats; Rats, Wistar; Solubility; Technology, Pharmaceutical

The objective was to investigate the suitable polymeric films for the development of diltiazem hydrochloride (diltiazem HCl) transdermal drug delivery systems. Hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC) were used as hydrophilic and hydrophobic film formers, respectively. Effects of HPMC/EC ratios and plasticizers on mechanical properties of free films were studied. Effects of HPMC/EC ratios on moisture uptake, in vitro release and permeation through pig ear skin of diltiazem HCl films were evaluated. Influence of enhancers including isopropyl myristate (IPM), isopropyl palmitate (IPP), N-methyl-2-pyrrolidone, oleic acid, polyethylene glycol 400, propylene glycol, and Tween80 on permeation was evaluated. It was found that addition of EC into HPMC film produced lower ultimate tensile strength, percent elongation at break and Young's modulus, however, addition of EC up to 60% resulted in too hard film. Plasticization with dibutyl phthalate (DBP) produced higher strength but lower elongation as compared to triethyl citrate. The moisture uptake and initial release rates (0-1 h) of diltiazem HCl films decreased with increasing the EC ratio. Diltiazem HCl films (10:0, 8:2 and 6:4 HPMC/EC) were studied for permeation because of the higher release rate. The 10:0 and 8:2 HPMC/EC films showed the comparable permeation-time profiles, and had higher flux values and shorter lag time as compared to 6:4 HPMC/EC film. Addition of IPM, IPP or Tween80 could enhance the fluxes for approx. three times while Tween80 also shorten the lag time. In conclusion, the film composed of 8:2 HPMC/EC, 30% DBP and 10% IPM, IPP or Tween80 loaded with 25% diltiazem HCl should be selected for manufacturing transdermal patch by using a suitable adhesive layer and backing membrane. Further in vitro permeation and in vivo performance studies are required.

Topics: Administration, Cutaneous; Animals; Calcium Channel Blockers; Cellulose; Chemistry, Pharmaceutical; Citrates; Delayed-Action Preparations; Dibutyl Phthalate; Diffusion; Diffusion Chambers, Culture; Diltiazem; Dosage Forms; Drug Carriers; Drug Compounding; Hypromellose Derivatives; Kinetics; Methylcellulose; Models, Chemical; Myristates; Palmitates; Permeability; Plasticizers; Polysorbates; Skin; Skin Absorption; Solubility; Swine; Technology, Pharmaceutical; Tensile Strength; Water

The purpose of this study was to examine a level A in vitro-in vivo correlation (IVIVC) for glipizide hydrophilic sustained-release matrices, with an acceptable internal predictability, in the presence of a range of formulation/manufacturing changes. The effect of polymeric blends of ethylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, xanthan gum, guar gum, Starch 1500, and lactose on in vitro release profiles was studied and fitted to various release kinetics models. Water uptake kinetics with scanning electron microscopy (SEM) was carried out to support the drug release mechanism. An IVIVC was established by comparing the pharmacokinetic parameters of optimized (M-24) and marketed (Glytop-2.5 SR) formulations after single oral dose studies on white albino rabbits. The matrix M-19 (xanthan:MCC PH301 at 70:40) and M-24 (xanthan:HPMC K4M:Starch 1500 at 70:25:15) showed the glipizide release within the predetermined constraints at all time points with Korsmeyer-Peppas' and zero-order release mechanism, respectively. Kopcha model revealed that the xanthan gum is the major excipient responsible for the diffusional release profile and was further supported by SEM and swelling studies. A significant level A IVIVC with acceptable limits of prediction errors (below 15%) enables the prediction of in vivo performance from their in vitro release profile. It was concluded that proper selection of rate-controlling polymers with release rate modifier excipients will determine overall release profile, duration and mechanism from directly compressed matrices.

Topics: Administration, Oral; Animals; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diffusion; Drug Carriers; Drug Compounding; Drug Stability; Excipients; Galactans; Glipizide; Hypoglycemic Agents; Hypromellose Derivatives; Kinetics; Lactose; Mannans; Methylcellulose; Microscopy, Electron, Scanning; Models, Biological; Models, Chemical; Plant Gums; Polysaccharides, Bacterial; Rabbits; Reproducibility of Results; Solubility; Starch; Tablets; Technology, Pharmaceutical; Water

We developed and optimized a novel pseudoephedrine hydrochloride (PSE) sustained-release dosage form. The system comprises immediate-release mini-tablets (IRMT) and sustained-release mini-tablets (SRMT) contained in a hydroxypropyl methylcellulose (HPMC) capsule. The IRMT contained PSE, excipients and low-substituted hydroxypropyl cellulose (a disintegrant), and the tablets were coated with HPMC, a water-soluble polymer. IRMT prepared with varying amounts of low-substituted hydroxypropyl cellulose all dissolved completely within the first 60min, so low-substituted hydroxypropyl cellulose content does not greatly influence PSE release. The SRMT contained only PSE and excipients, and were coated with a mixture of HPMC and the water-insoluble polymer ethylcellulose. The PSE release profile for the SRMT could be controlled by varying the thickness of the coat, and the lag time could be controlled by varying the amount of ethylcellulose present in the polymer coat. PSE was released immediately from our encapsulated mini-tablet system and release was sustained over an extended period of time: the PSE in the IRMT dissolved within 60min, whereas the PSE in the SRMT was released over 8-10h. This system can be modified to yield various extended drug-release profiles, thereby harnessing the benefits of both SRMT and IRMT.

Topics: Capsules; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Excipients; Hypromellose Derivatives; Methylcellulose; Nasal Decongestants; Pseudoephedrine; Solubility; Tablets; Time Factors

The aim of the study was to provide a controlled release system, which could be used for the oral administration of highly water-insoluble drugs. Pellets have been prepared by extrusion/spheronization containing two model drugs (methyl and propyl parabens) of low water solubility. One type of pellets contained the drugs mixed with lactose and microcrystalline cellulose (MCC) and the other types of pellets contained the model drugs dissolved in a self-emulsifying system (4.8%) consisting of equal parts of mono-diglycerides and polysorbate 80 and MCC. Pellets of all types in the same size fraction (1.4-2.0 mm) were coated to different levels of weight gain, with ethylcellulose, talc and glycerol. A sample of pellets containing methyl parabens in the self-emulsifying system was pre-coated with a film of hydroxypropylmethyl cellulose from an aqueous solution and then coated as above. Dissolution experiments established that the presence of the self-emulsifying system enhanced the drug release of both model drugs and that the film coating considerably reduced the drug release from pellets made with just water, lactose and MCC. The coating reduced the drug release from the pellets containing the self-emulsifying system to a lesser extent but in relation to the quantity of coat applied to the pellets. The application of a sub-coating of hydroxypropylmethyl cellulose was able to reduce the release rate of methyl parabens self-emulsifying system ethyl cellulose coated pellets. Thus, the formulation approach offers the possibility of formulating and controlling the in vitro release of water-insoluble drugs from solid oral dosage forms.

Topics: Capsules; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diglycerides; Emulsions; Excipients; Hypromellose Derivatives; Lactose; Methylcellulose; Monoglycerides; Parabens; Particle Size; Pharmaceutical Preparations; Polysorbates; Solubility; Technology, Pharmaceutical; Time Factors; Water

Films of pure ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) polymers and EC/HPMC blends were prepared from solutions by spin coating where isopropyl alcohol (IPA), water, and IPA/water cosolvent were used as solvents. Surface structures of the films were investigated using optical microscopy, atomic force microscopy (AFM), and Raman mapping and spectroscopy. For the films prepared from EC/HPMC blend solutions using the IPA/water cosolvent, different domain structures such as islands or pits and phase separation between EC and HPMC were observed by optical microscopy and AFM. The nature of the polymer components on the surface of the films was identified by Raman mapping and spectroscopy. Experimental results also indicated that polymer composition, solvent, and temperature during spin coating had significant impacts on surface structures of the films.

Topics: Cellulose; Chemistry, Physical; Hypromellose Derivatives; Membranes, Artificial; Methylcellulose; Microscopy, Atomic Force; Microscopy, Video; Polymers; Solubility; Solvents; Spectrum Analysis, Raman; Surface Properties; Temperature

The present study investigates if drug diffusion through plasticized isolated ethylcellulose (EC)/hydroxypropyl methylcellulose (HPMC) films prepared by solvent casting can be used as a tool to develop spray-coated dosage forms. In particular, the importance of the level and type of plasticizers was investigated. The permeability of the model drug metoprolol tartrate through plasticized isolated films could be adjusted by selecting the type and amount of plasticizer in the films due to the different hydrophilicity of the plasticizers. The release of metoprolol tartrate from coated pellets is consistent with the drug diffusion through the films made up of the same polymer blends. This indicated that it is useful to test isolated films for early predictions and for formulation optimization.

Topics: Cellulose; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Diffusion; Equipment Design; Hypromellose Derivatives; Methylcellulose; Metoprolol; Permeability; Plasticizers; Polymers; Technology, Pharmaceutical; Time Factors

Complex tablets with zero-order drug release characteristics were fabricated using three-dimensional printing processes. The matrix tablets exhibited material gradients in radial direction and had drug-free release-barrier layers on both bases. The content of model drug acetaminophen incorporated in the tablets through premixing reached up to 68% of the tablets' weight. Tablets with ethylcellulose gradients showed acceptable mechanical and pharmacotechnical properties, as indicated by crushing strength, friability, and content uniformity tests. The structure and the gradients of ethylcellulose in the tablets were envisaged through environmental scanning electron microscopy and fluorescence tracing technique. Erosion and dissolution studies in vitro indicated that drug was released via a two-dimensional surface erosion mechanism, and 98% of the drug could be released linearly in 12 h. Tablets with other release-retardation material gradients such as sodium lauryl sulfate, stearic acid, and Eudragit RS-100 showed similar release-retardation effects by different release-retardation mechanisms. Through the printing of release-retardation materials, 3DP processes could easily prepare tablets with high dosage and special design features for furnishing the desired drug release characteristics.

Topics: Acetaminophen; Acrylic Resins; Algorithms; Analgesics, Non-Narcotic; Cellulose; Delayed-Action Preparations; Drug Compounding; Excipients; Hypromellose Derivatives; Methylcellulose; Microscopy, Electron, Scanning; Particle Size; Sodium Dodecyl Sulfate; Solubility; Stearic Acids; Surface Properties; Surface-Active Agents; Tablets

The purpose of this study was to develop and optimize oral controlled-release formulations for tamsulosin hydrochloride using a combination of two cellulose ester derivatives, hydroxypropyl methylcellulose (HPMC) and hydroxypropyl methylcellulose phthalate (HPMCP), with Surelease as a coating material. A three-factor, three-level Box-Behnken design was used to prepare systematic model formulations, which were composed of three formulation variables, the content of HPMC (X(1)) and HPMCP (X(2)) and the coating level (X(3)), as independent variables. The response surface methodology (RSM) and multiple response optimization utilizing the polynomial equation were used to search for the optimal coating formulation with a specific release rate at different time intervals. The drug release percentages at 2, 3 and 5h were the target responses and were restricted to 15-30% (Y(1)), 50-65% (Y(2)) and 80-95% (Y(3)), respectively. The optimal coating formulation was achieved with 10% HPMC and 20% HPMCP at a coating level of 25%, and the observed responses coincided well with the predicted values from the RSM optimization technique. The drug release from pellets coated with the optimized formulation showed a controlled-release pattern (zero-order), in comparison with a commercial product (Harunal capsule). In conclusion, a novel, oral, controlled-release delivery system for tamsulosin hydrochloride was successfully developed by incorporating HPMC and HPMCP as coating additives into Surelease aqueous ethylcellulose dispersion.

Topics: Administration, Oral; Adrenergic alpha-Antagonists; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Factor Analysis, Statistical; Hypromellose Derivatives; Kinetics; Methylcellulose; Models, Chemical; Solubility; Sulfonamides; Tamsulosin; Technology, Pharmaceutical

A floating granular delivery system consisting of calcium silicate (CS) as porous carrier; repaglinide (Rg), an oral hypoglycemic agent; and hydroxypropyl methylcellulose K4M (HPMC K4M), ethyl cellulose (EC) and carbopol 940 (CP940) as matrix forming polymers was prepared and evaluated for its gastro-retentive and controlled release properties. The effect of various formulation and process variables on the particle morphology, micromeritic properties, in vitro floating behavior, drug content (%) and in vitro drug release was studied. The transit of floating granules of optimized formulation in the gastrointestinal (GI) tract was monitored by gamma scintigraphy in albino rabbits. The optimized formulation was compared in vivo with lactose granules (RgSCLG) prepared from identical polymers with their optimized composition ratio. Repaglinide-loaded optimized formulation was orally administered to albino rabbits and blood samples collected were used to determine pharmacokinetic parameters of Rg from floating granular formulation. Results were compared with pharmacokinetic parameters of marketed tablet formulation of Rg. The optimized formulation (RgSCG4) demonstrated favorable in vitro floating and release characteristics. Prolonged gastric residence time (GRT) of over 6 hr was achieved in all subjects for calcium silicate based floating granules of Rg. The relative bioavailability of Rg-loaded floating granules increased 3.8-fold in comparison to that of its marketed capsule. The designed system, combining excellent buoyant ability and suitable drug release pattern, offered clear advantages in terms of increased bioavailability of repaglinide.

Topics: Acrylic Resins; Administration, Oral; Animals; Biological Availability; Calcium Compounds; Carbamates; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Gastrointestinal Transit; Hypoglycemic Agents; Hypromellose Derivatives; Male; Methylcellulose; Particle Size; Piperidines; Polymers; Porosity; Rabbits; Radionuclide Imaging; Silicates

Blends of Eudragit E (EE) and polymeric excipients using thermal analysis and FTIR spectroscopy were examined. The interactions amongst the blend components were quantified in terms of parameters K1 and K2 in Schneider equation and were explained on the basis of interactions between the functional groups of the blend constituents investigated by FTIR spectroscopy. EE formed miscible blends with EC and polyelectrolyte complexes increasing in strength in the order: ES

Topics: Calorimetry, Differential Scanning; Cellulose; Hydrogen-Ion Concentration; Methylcellulose; Polymethacrylic Acids; Spectroscopy, Fourier Transform Infrared; Zein

The present study involved the preparation of ibuprofen-containing controlled release tablets formulated from either the established granular product, Ethocel Standard Premium, or the novel finely-milled product, Ethocel Standard FP Premium. The tablets were prepared by either direct compression or wet granulation. The aim was to explore the influence of different parameters on the kinetics and mechanisms of ibuprofen release from the tablets. These parameters were; polymer particle size, polymer molecular weight, drug : polymer ratio, preparation methodology and partial replacement of lactose with the coexcipient-hydroxypropyl methylcellulose (HPMC). The derived drug release data were analyzed with reference to various established mathematical models while the f2-metric technique was used in order to determine profile equivalency. It was found that drug release was mostly modulated by several interactive factors apparently exhibiting crosstalk. Nevertheless, it was possible to identify some simple rules. Incorporation of Ethocel FP polymers and application of the wet granulation technique facilitated greater efficiency in controlling ibuprofen release behavior from the matrices. Furthermore, drug release profiles could be modulated by partial substitution of the primary excipient with HPMC. Polymer concentrations and particle sizes, rather than viscosity grade, were found to be decisive factors in controlling drug release rates.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Ethers; Excipients; Ibuprofen; Kinetics; Lactose; Methylcellulose; Particle Size; Solubility; Tablets; Viscosity

The objective of this study was to investigate the influence of various water-soluble additives and HPMCP as an enteric polymer into Surelease for the developement of oral controlled release system containg tamsulosin hydrochloride. The drug loaded pellets were coated with only Surelease or Surelease containing HPMC, PEG 4000, mannitol and HPMCP (20% w/w). In case of HPMC and PEG 4000 as additives into Surelease film, the rapid drug release was observed in pH 1.2 while the higher drug release was achieved by adding HPMCP into Surelease as well as by increasing the amount of HPMCP (10, 20, and 30% w/w) in pH 7.2. The incorporation of HPMCP into Surelease showed pH-denpendent drug release due to its pH-dependent nature. Therefore, the incorporation of HPMCP into Surelease based on aqueous coating formulation is an effective way to develop oral controlled release delivery systems containing tamsulosin hydrochloride.

Topics: Cellulose; Delayed-Action Preparations; Drug Compounding; Drug Implants; Excipients; Methylcellulose; Solubility; Sulfonamides; Tamsulosin; Time Factors; Water

Ethylcellulose/methylcellulose blends were produced using different precipitation techniques and impregnated with naproxen, a non-steroidal anti-inflammatory drug (NSAID). Solvent-evaporation technique was used not only for the preparation of ethylcellulose/methylcellulose microspheres but also to encapsulate naproxen. Supercritical fluid (SCF) impregnation was also performed to prepare naproxen loaded microspheres. The microspheres, impregnated by the SCF technique, were prepared both by solvent-evaporation and by a supercritical antisolvent (SAS) process. In vitro release profiles at pH 7.4 and 1.2, of naproxen-loaded microspheres were evaluated and the results were modelled Fick's law of diffusion and Power law. Miscrospheres prepared by supercritical antisolvent have a higher loading capacity and present a slower release profile. The systems studied present a release mechanism controlled by drug diffusion which complies Fick's law of diffusion.

Topics: Anti-Inflammatory Agents; Body Fluids; Carbon Dioxide; Cellulose; Delayed-Action Preparations; Diffusion; Hydrogen-Ion Concentration; Kinetics; Methylcellulose; Microspheres; Naproxen; Particle Size; Solubility; Solvents; Surface Properties; Technology, Pharmaceutical; Volatilization

The supercritical antisolvent (SAS) technique was used to prepare ethyl cellulose/methyl cellulose blends, two biocompatible polymers commonly used as drug carriers in controlled delivery systems. Ethyl cellulose is widely used as a drug carrier. The drug release of the delivery devices can be controlled to some extent by addition of a water-soluble or water swellable polymer, such as methyl cellulose. This leads to the solubility enhancement of poorly water-soluble molecules. SAS experiments were carried out at different operational conditions and microspheres with mean diameters ranging from 5 to 30 microm were obtained. The effect of CO(2) and liquid flow, temperature and pressure on particle size and particle size distribution was evaluated. The microspheres were precipitated from a mixture of dichloromethane (DCM) and dimethylsulfoxide (DMSO) (4:1 ratio). The best process conditions for this mixture were according to our study 40 degrees C and 80 bar.

Topics: Cellulose; Chemical Precipitation; Chromatography, Supercritical Fluid; Dimethyl Sulfoxide; Drug Carriers; Methylcellulose; Methylene Chloride; Microspheres; Polymers; Pressure; Solvents; Surface Properties; Technology, Pharmaceutical; Temperature

Directly compressed mini tablets were produced containing either hydroxypropylmethylcellulose (HPMC) or ethylcellulose (EC) as release controlling agent. The dynamics of water uptake and erosion degree of polymer were investigated. By changing the polymer concentration, the ibuprofen release was modified. In identical quantities, EC produced a greater sustaining release effect than HPMC. Different grades of viscosity of HPMC did not modify ibuprofen release. For EC formulations, the contribution of diffusion was predominant in the ibuprofen release process. For HPMC preparations, the drug release approached zero-order during a period of 8 h. For comparative purposes, tablets with 10 mm diameter were produced.

Topics: Cellulose; Delayed-Action Preparations; Hypromellose Derivatives; Ibuprofen; Methylcellulose; Solubility; Tablets; Technology, Pharmaceutical; Viscosity

The objective of this study was to develop controlled release matrix embedded formulations of celecoxib (CCX) as candidate drug using hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC), either alone or in combination, using optimization techniques like polynomial method and composite design. This would enable development of controlled release formulations with predictable and better release characteristics in lesser number of trials. Controlled release matrix tablets of CCX were prepared by wet granulation method. The in vitro release rate studies were carried out in USP dissolution apparatus (paddle method) in 900 ml of sodium phosphate buffer (pH 7.4) with 1% v/v tween-80. The in vitro drug release data was suitably transformed and used to develop mathematical models using first order polynomial equation and composite design techniques of optimization. In the formulations prepared using HPMC alone, the release rate decreased as the polymer proportion in the matrix base was increased. Whereas in case of formulations prepared using EC alone, only marginal difference was observed in the release rate upon increasing the polymer proportion. In case of formulations containing combination of HPMC and EC, the release of the drug was found to be dependent on the relative proportions of HPMC and EC used in the tablet matrix. The release of the drug from these formulations was extended up to 21 h indicating they can serve as once daily controlled release formulations for CCX. Mathematical analysis of the release kinetics indicates a near approximate Fickian release character for most of the designed formulations. Mathematical equation developed by transforming the in vitro release data using composite design model showed better correlation between observed and predicted t(50%) (time required for 50% of the drug release) when compared to first order polynomial equation model. The equation thus developed can be used to predict the release characteristics of the drug from matrix embedded formulations depending upon the proportion of HPMC and EC used in the formulation.

Topics: Celecoxib; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Lactose; Methylcellulose; Pyrazoles; Solubility; Sulfonamides; Tablets; Technology, Pharmaceutical

Compressed mini-tablets systems are presented as a biphasic delivery system designed for zero-order sustained drug release. The outer layer that fills the void spaces between the mini-tablets was formulated to release the drug in a very short time (fast release), while the mini-tablets provided a prolonged release. Different composition (HPMC or EC) and number (10 or 21) of mini-tablets were used to obtain different drug release rates. The in vitro performance of these systems showed the desired biphasic behaviour: the drug contained in the fast releasing phase (powder enrobing the mini-tablets) dissolved within the first 2 min, whereas the drug contained in the mini-tablets was released at different rates, depending up on formulation. Based on the release kinetic parameters calculated, it can be concluded that mini-tablets containing HPMC were particularly suitable approaching to zero-order (constant) release over 8h time periods.

Topics: Algorithms; Carboxymethylcellulose Sodium; Cellulose; Drug Compounding; Drug Delivery Systems; Excipients; Hypromellose Derivatives; Ibuprofen; Kinetics; Methylcellulose; Models, Chemical; Porosity; Tablets; Tensile Strength

The present study was conducted to investigate the low viscosity grades of hydroxypropylmethyl cellulose (HPMC) and ethyl cellulose (EC) in sustaining the release of water insoluble drug, naproxen from the matrix tablets. Both HPMC and EC were incorporated in the matrix system separately or in combinations by wet granulation technique. In vitro dissolution studies indicated that EC significantly reduced the rate of drug release compared to HPMC in 12 hour testing time. But, no significant difference was observed in the release profiles of matrix tablets made by higher percentages of EC. The tablets prepared with various combinations of HPMC and EC also failed to produce produce the desired release profiles. However, comparatively linear and desirable sustained release was obtained from EC-based matrix tablets prepared by slightly modifying the granulation method. Moreover, two different compression forces used in tableting had no remarkable effect on the release profile of naproxen.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Delayed-Action Preparations; Drug Delivery Systems; Excipients; Hardness; Hypromellose Derivatives; Methylcellulose; Naproxen; Solubility; Viscosity

The aim of the present study was to develop a delivery system wherein the retention of ofloxacin could be achieved for increased local action in gastric region against Helicobacter pylori infection. The formulation was optimized on the basis of in vitro buoyancy and in vitro release in citrate phosphate buffer (pH 3). The hydrodynamically balanced capsules were prepared by physical mixing of various grades of HPMC and poly(ethylene oxide) (PEO) alone as well as in combinations. Cellulose acetate pthalate, liquid paraffin, and ethyl cellulose were used as release modifiers so as to maintain release of drug over a period of 12 h. The capsules prepared with PEOWSR 60K and drug coated with 2.5% ethyl cellulose gave the best in vitro percentage release and were taken as the optimized formulations. Various grades of Eudragit and PEO were used in combination for formulating floating microspheres using solvent diffusion technique for preparation of multiple unit system. The use of two different solvents (dichloromethane and ethanol) that differed in the rate of diffusion led to formation of a hollow core in the microspheres, which was partially responsible for the flotation ability. The in vitro release of the floating capsules and microspheres was found to be 96.02% and 95.83% in 12 h, respectively. Both the dosage forms follow Higuchi model for release from formulations. By fitting the in vitro release data of single unit dosage form into zero-order, first-order, and Higuchi model, it could be concluded that the release followed Higuchi model, as the correlation coefficient (R2 value) was higher than those in the other two release models. In both cases of single and multiple unit dosage form, R2 values for Higuchi model were found to be good, showing that drug release followed non-Fickian diffusion mechanism.

Topics: Administration, Oral; Anti-Bacterial Agents; Biological Availability; Capsules; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diffusion; Digestive System; Drug Stability; Ethylene Glycol; Ethylene Oxide; Hypromellose Derivatives; Methylcellulose; Microspheres; Mineral Oil; Ofloxacin; Particle Size; Polymers; Polymethacrylic Acids; Porosity; Solubility; Time Factors

To prepare verapamil hydrochloride controlled-onset extended-release pellets (VH-COERP) and study its release behavior in vitro. To compare the pharmacokinetic characteristics and bioavailability in six Beagle dogs after oral administration of VH-COERP and verapamil hydrochloride delayed-release pellets (VH-DRP) as reference.. The core of VH-COERP were prepared in the fluidized bed (mini-glatt) by spraying water solution containing drugs onto sucrose-starch pellets with hydroroxy propyl methyl cellulose (HPMC) as the inner coating swelling layer and ethylcellulouse aqueous dispersion as the outer coating controlled layer. Through modifying the coating level of inner and outer layer, the VH-COERP with the optimized cumulative release profile was obtained. The concentration of VH in plasma of six dogs and its pharmacokinetic behaviors after oral administration of VH-COERP and VH-DRP at different times were studied by RP-HPLC. The pharmacokinetic parameters were computed by software program 3P97.. The lag time, the release behavior and the amount of VH from VH-COERP within 24 hours were not influenced by the pH of dissolution medium and post-process, but obviously influenced by the different kinds of added material in swelling layer and the coating level of the inner swelling layer and the outer controlled layer. In vitro the lag time of release profile of VH from VH-COERP was 5 h and then VH was extended release from VH-COERP in the following time. Compared with the VH-DRP, VH-COERP in vivo has an obviously lag time (4 h) , Tmax was also delayed (8 h) and the relative bioavailability was (94.56 +/- 7.64)%.. The release profile of VH from VH-COERP was shown to be extended-release after an conspicuous lag time in vitro and in vivo. So the drug can be taken by the patient before bed time and begin to work at the morning.

Topics: Administration, Oral; Animals; Biological Availability; Calcium Channel Blockers; Cellulose; Delayed-Action Preparations; Dogs; Drug Stability; Hypromellose Derivatives; Methylcellulose; Microscopy, Electron, Scanning; Verapamil

The objective of the present investigation was to prepare and evaluate floating granular delivery system consisting of (i) calcium silicate (CS) as porous carrier; (ii) ranitidine hydrochloride (RH), an anti-ulcer agent; and (iii) hydroxypropyl methylcellulose K4M (HPMC) and ethylcellulose (EC) as matrix forming polymers. The effect of various formulation and process variables on the particle morphology, particle size, micromeritic properties, percent drug content, in vitro floating behavior, and in vitro drug release from the floating granules was studied. The scanning electron microscopy (SEM) of granules revealed that that more pores of CS in secondary coated granules (SCG) were covered by the polymer film than those in primary coated granules (PCG). The formulation demonstrated favorable in vitro floating and drug release characteristics. The in vivo evaluation for the determination of pharmacokinetic parameters was performed in albino rats. Higher plasma concentration was maintained throughout the study period from the floating granules of RH. The enhanced bioavailability and elimination half-life observed in the present study may be due to the floating nature of the dosage form. The results suggested that CS is a useful carrier for the development of floating and sustained release preparations.

Topics: Animals; Anti-Ulcer Agents; Biological Availability; Calcium Compounds; Cellulose; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Hypromellose Derivatives; Male; Methylcellulose; Microscopy, Electron, Scanning; Porosity; Ranitidine; Rats; Silicates; Solubility; Surface Properties

A polymer matrix system for transdermal delivery of atenolol was developed for its prolonged and controlled release using different ratios of ethylcellulose and hydroxypropyl methylcellulose. These polymeric matrix films were characterized for thickness, tensile strength, moisture content and drug content. They were also studied for in vitro drug release and in vitro drug skin permeation. The drug release from the films was found to be Fickian diffusion type and exhibiting linear relationship between drug release (Q) vs. square root of time (t0.5). The in vitro skin permeation of drug from transdermal drug delivery system (TDDS) was evaluated using dermatomed pig skin. The product which shows in vitro drug skin permeation near to 64 mcg/h/ml was selected for in vivo studies. The in vivo studies revealed that Ma EC HPMC 46 is most effective among the other polymeric matrix TDDS. The AUC0-28 with Ma EC HPMC 46 was better than orally administered conventional doses at twelve hours interval (AUC0-28 1587 ng h/ml) as well as no trough and peaks in drug plasma level was recorded with TDDS. Hence, it could be concluded that the designed polymeric matrix TDDS of atenolol could be used successfully for effective and prolonged delivery of atenolol. However, it further demands exploration in clinic, an insight vision towards the development of TDDS for commercial use.

Topics: Administration, Cutaneous; Adrenergic beta-Antagonists; Animals; Atenolol; Cellulose; Chemistry, Pharmaceutical; Diffusion; Drug Compounding; Drug Stability; Excipients; Hypromellose Derivatives; In Vitro Techniques; Methylcellulose; Rabbits; Skin; Skin Absorption; Solubility; Swine; Tensile Strength

Microcapsules for sustained release of poorly soluble isosorbide dinitrate (ISDN) were prepared based on ethylcellulose (EC) and/or blended with appropriate amounts of relatively hydrophilic hydroxypropyl cellulose (HPC) as matrix materials using the oil-in-oil emulsion evaporation method. The microspheres studied had three-mode sizes (100-150, 250-300 and 400-450 microm) and four polymer compositions (1, 0.833, 0.67 and 0.5 weight fraction EC). The microspheres were observed to contain essentially no drug crystalline domain and were of a porous morphology. The cumulative amounts of ISDN releasing from the microspheres as functions of mode fractions size and polymer compositions were measured in vitro. It was observed that the microspheres' size influenced the release behaviour of drug more obviously than the polymer composition. The smaller size and the higher hydrophilic HPC content show the faster release rate of drug and the smaller amount of drug residue. The kinetics of drug release depends on the size and polymer composition. The microspheres with 100-150 microm, of all polymer compositions, present one-stage diffusion kinetic with a lag period for drug release. On the other hand, the microspheres with the other two sizes exhibit two-stage diffusion kinetic with a lag period. According to the kinetic model, the microspheres obtained are surmised to have a core-shell like drug concentration distribution and/or a core-shell morphology.

Topics: Cellulose; Delayed-Action Preparations; Diffusion; Drug Compounding; Excipients; Hypromellose Derivatives; Isosorbide Dinitrate; Kinetics; Methylcellulose; Microscopy, Electron, Scanning; Microspheres; Particle Size; Porosity; Solubility; Spectrophotometry, Ultraviolet; Vasodilator Agents

This study was to optimize the coating level in the development of controlled release pellets coated with Surelease and neutralized hydroxypropyl methylcellulose phthalate (HPMCP) by a computer optimization technique based on a response surface methodology utilizing polynomial equation. A full factorial 3(2) design was used for the optimization procedure with coating level (X(1)) and HPMCP content (X(2)) as the independent variables. The drug release percent at 2, 3 and 5 h were the target responses, which were restricted to 12-39% (Y(1)), 44-70% (Y(2)) and 70-100% (Y(3)), respectively. The quadratic model was well fitted to the data, and the resulting equation was used to predict the responses in the optimal region. It was shown that the optimized coating formulation was achieved at the ratio of 3:1 (Surelease: neutralized HPMCP) with 20% coating level. The optimized formulation showed release profiles and responses, which were close to predicted responses. Therefore, a full factorial 3(2) design and optimization technique can be successfully used in the development of optimized coating formulations based on Surelease and neutralized HPMCP to achieve a controlled release drug delivery system containing tamsulosin hydrochloride.

Topics: Adrenergic alpha-Antagonists; Algorithms; Cellulose; Delayed-Action Preparations; Drug Compounding; Hydrogen-Ion Concentration; Methylcellulose; Particle Size; Software; Sulfonamides; Surface Properties; Tamsulosin

Blends of aqueous dispersions of a water-insoluble and an enteric polymer, namely ethyl cellulose:hydroxypropyl methylcellulose acetate succinate (EC:HPMCAS) and ethyl cellulose:methacrylic acid ethyl acrylate copolymer (EC:Eudragit L), were used as coating materials to control theophylline release from matrix pellets. Varying the polymer blend ratio, broad ranges of drug release patterns were obtained at low as well as at high pH. Interestingly, the resulting release profiles were rather similar for both types of blends in 0.1 M HCl, whereas significant differences were observed in phosphate buffer pH 7.4. Surprisingly, drug release at high pH was much slower for EC:HPMCAS blends compared to EC:Eudragit L blends, although HPMCAS leached out more rapidly (and to a higher extent) from the film coatings than Eudragit L. To explain these phenomena and to better understand the underlying drug release mechanisms, thin polymeric films of identical composition as the pellet coatings were prepared and physicochemically characterized before and upon exposure to the release media. Importantly, the polymer particle size was identified to be a very crucial formulation parameter, determining the resulting film coating structure and properties. The Eudragit L particles are much smaller than the HPMCAS particles (nano- vs. micrometer size range) and, thus, more effectively hinder the formation of a continuous and mechanically stable EC network. Consequently, the EC structures remaining after enteric polymer leaching at high pH are mechanically much weaker in the case of Eudragit L. Upon exposure to phosphate buffer, water-filled cracks are formed, through which the drug rapidly diffuses out. In contrast, the EC structures remaining upon HPMCAS leaching are mechanically stronger and drug release is controlled by diffusion through the polymeric remnants.

Topics: Cellulose; Chemical Phenomena; Chemistry, Physical; Chromatography, High Pressure Liquid; Dosage Forms; Drug Carriers; Drug Stability; Emulsions; Hardness Tests; Kinetics; Methylcellulose; Microscopy, Electron, Scanning; Particle Size; Plasticizers; Polymers; Polymethacrylic Acids; Surface Properties; Theophylline

Silica gel was used as core particles to design a simple preparation for controlled delivery system with a high drug content. Drug loading was carried out by immersing the silica gel in a pre-heated drug solution or suspension. HPLC, SEM, DSC, PXRD analysis and N2 adsorption studies evaluated the drug-loading process. In the next step, the drug-loaded silica gel was coated with hydroxypropyl methylcellulose (HPMC) and an aqueous dispersion of ethylcellulose (Aquacoat) to control the drug release. The release profile was determined using a dissolution test. The results showed that silica gel could adsorb great quantities of the drug, up to about 450 mg/g, by repetition of the loading process. Evaluation of the drug-loading process indicates that drug deposition in the pores occurs during the loading process and the drug-loading efficacy is strongly related to the drug solubility. On the other hand, the dissolution test showed that the drug release could be controlled by polymer coating the drug-loaded silica gel. An HPMC undercoating effectively suppresses the drug release, as it smoothes the drug-loaded core surface and aids in the formation of a continuous Aquacoat coating film. The floating property was also observed during the dissolution test.

Topics: Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Carriers; Drug Stability; Gels; Methylcellulose; Polyethylene Glycols; Porosity; Silica Gel; Silicon Dioxide; Solubility; Surface-Active Agents; Theophylline; Time Factors

The purpose of this study is to investigate the release mechanism of poorly water-soluble drug from the extended release solid dispersion systems with water-insoluble ethylcellulose (EC) and water-soluble hydroxypropylmethylcellulose (HPMC) (1:1). Indomethacin (IND) was used as a model of poorly water-soluble drug. Two kinds of solid dispersions were prepared by the solvent evaporation methods, which consist of the same formulation but exhibit different physical performance. It appeared that the dissolution behavior of IND depended on the structures of EC-HPMC matrices, which were governed by the preparation method. In addition, the dissolution behavior showed pH dependency that the dissolution rate of IND was slower in acidic medium than that in neutral medium. The experimental results revealed that the hydrophobic interaction between IND and EC occurred under lower pH and strongly delayed the dissolution rate of IND. The relationship between this hydrophobic interaction and the dissolution rate of IND was also proposed.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Delayed-Action Preparations; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; Indomethacin; Methylcellulose; Microscopy, Electron, Scanning; Powders; Solubility; Spectroscopy, Fourier Transform Infrared; Water; X-Ray Diffraction

Nowadays, oral dosage forms with controlled release kinetics have known an increasing interest. The polymer coating of drug-loaded particles is one of the most common methods used for controlling drug delivery. Such multilayered particles could be either filled into capsules or compressed into tablets for their oral administration. However, many studies have noticed that coating films are damaged during the compression process, leading to significant changes in drug release profiles. The aims of this study were to investigate the effects of a thin cushioning layer [made of HydroxyPropylMethyl Cellulose (HPMC)] applied on coated theophylline particles upon particle characteristics, tablet properties, and then upon their dissolution performance. If no significant effect was shown with particles, this thin HPMC layer played an important role in the tablets. Tablet cohesiveness was decreased due to HPMC cushioning properties and moreover, the theophylline release rate was increased, as HPMC is a water-soluble polymer creating channels in polymer film for dissolution medium. Therefore, a cushioning layer helped to protect polymer coats from fracture during compression but could also affect drug release and so, both effects must be checked in such a drug delivery system.

Topics: Cellulose; Chemistry, Pharmaceutical; Drug Compounding; Excipients; Hypromellose Derivatives; Methylcellulose; Solubility; Tablets, Enteric-Coated; Theophylline

The objective of the study was to develop a sustained release system consisting of a hot-melt extruded ethylcellulose pipe surrounding a drug-containing hydroxypropyl methylcellulose (HPMC)-Gelucire 44/14 core, yielding a monolithic matrix system applicable in the domain of sustained drug release. The influence of HPMC substitution type and viscosity grade was investigated through dissolution testing and erosion studies. All sustained release systems showed a nearly constant drug release profile with only 40% of the drug released after 24 h. To achieve complete drug release after 24 h, the core formulation and the dimensions of the hollow pipe were modified. Changing the composition of the core did not result in the intended zero-order drug release. Shortening the length of the ethylcellulose cylinder accelerated drug release, while modifying the diameter did not affect the drug release rate. The drug dissolution profile and the release mechanism were independent of drug solubility. Increasing the drug loading caused a small increase of the drug release rate, but did not alter the release mechanism.

Topics: Cellulose; Drug Delivery Systems; Lactose; Methylcellulose; Oxazines; Polyethylene Glycols

As a matter of fact, in vitro dissolution is well known to be the method of choice for the pharmaceutical industry to develop effective medicines. However, many experiments must be performed all along a new product life and they represent an overcharge of work for researchers. The purpose of this paper was to assess the relevance of new parameters obtained during preformulation stage by Nuclear Magnetic Resonance (NMR) experiments to better understand drug release mechanism. This study was carried out with three cellulose derivatives currently used as carrier matrices (Microcrystalline cellulose (MCC), Hydroxypropylmethyl cellulose (HPMC) and Ethyl cellulose (EC)). Granules and tablets were produced with these three excipients (60% w/w) and theophylline as drug model (40%). On the one hand, in vitro dissolution studies were performed with the rotating paddle method displaying the different release behaviour of these three matrices (immediate release for MCC, steady release for HPMC and sustained release for EC). On the other hand, the evolution of the T2m spin-spin relaxation time in NMR experiments during granules hydration was recorded. NMR findings shore up dissolution data, both depending on interactions between the matrix and water. NMR spectroscopy appears to be a valuable tool for obtaining, at an earlier stage of drug development, more information about drug release mechanism.

Topics: Algorithms; Cellulose; Chemistry, Pharmaceutical; Drug Carriers; Excipients; Hypromellose Derivatives; Magnetic Resonance Spectroscopy; Methylcellulose; Microscopy, Electron, Scanning; Pharmaceutical Preparations; Powders; Solubility; Tablets; Theophylline

A matrix-in-cylinder system for sustained drug delivery, consisting of a hot-melt extruded ethylcellulose (EC) pipe surrounding a drug containing HPMC-Gelucire 44/14 core, was evaluated in vitro and in vivo. In an aqueous medium, the HPMC-Gelucire core forms a gel plug, which releases the drug-through the open ends of the EC pipe--by means of erosion. The influence of hydrodynamic and mechanical stress and the effect of different 'physiologically relevant' dissolution media on the in vitro drug release were investigated. From these in vitro dissolution tests, it was concluded that the EC pipe has a protective effect on the drug containing HPMC-Gelucire core. It largely protects the core against hydrodynamics and mechanical stress. Furthermore, drug release from the matrix-in-cylinder system was only slightly affected by the composition of the dissolution medium. A randomised crossover in vivo study in dogs revealed that the matrix-in-cylinder system containing propranolol hydrochloride has an ideal sustained release profile with constant plasma levels maintained over 24 h. Moreover, administration of the matrix-in-cylinder system resulted in a 4-fold increase in propranolol bioavailability when compared with a commercial sustained release formulation (Inderal).

Topics: Administration, Oral; Animals; Biological Availability; Cellulose; Cross-Over Studies; Delayed-Action Preparations; Dogs; Drug Carriers; Hypromellose Derivatives; In Vitro Techniques; Male; Methylcellulose; Polyethylene Glycols; Propranolol; Random Allocation; Solubility; Stress, Mechanical; Technology, Pharmaceutical; Time Factors

The purposes of this study were to investigate the use of chitosan in the manufacture of beads by extrusion-spheronization without inclusion of microcrystalline cellulose, and to study the effect of formulation and process variables on the characteristics of the beads. Beads containing chitosan, fine particle ethylcellulose, hydroxypropyl methylcellulose (HPMC), and caffeine as the model drug were manufactured. Bead size, yield, shape, friability, density, porosity, and release studies were determined. Spherical beads with good mechanical properties could be manufactured without microcrystalline cellulose. Release studies showed that there was immediate release of drug from the beads. A five factor, half fraction screening design was employed to study the effect of formulation variables and process variables on the properties of the beads. Statistical analysis indicated that formulation variables such as the chitosan content, HPMC content, and water content, and process variables such as the spheronizer speed and extruder speed significantly affected the physical properties of the beads. The bead size decreased with an increase in chitosan content. Significant two-factor interactions exist between the variables for several of the measured responses. Beads with high percentage yield and high sphericity can be obtained at high chitosan content, and low HPMC content, water content, spheronizer speed, and extruder speed. Less friable beads can be obtained at high levels of studied formulation variables and low levels of studied process variables. Beads of high density and low porosity can be manufactured at high levels of the studied formulation and process variables. Regression equations were generated using Statgraphics Plus software that can be used to develop formulations with desired bead properties. Chitosan was useful to provide beads of acceptable physical properties using water as a granulating fluid in the extrusion-spheronization process.

Topics: Caffeine; Cellulose; Chitin; Chitosan; Drug Compounding; Drug Delivery Systems; Excipients; Hypromellose Derivatives; Methylcellulose; Particle Size; Porosity; Time Factors

The mechanical properties of polymer films used in pharmaceutical coatings of pulsatile drug delivery systems were evaluated in the dry and the wet state by a newly developed puncture test, which allowed the time-dependent measurement of the mechanical properties on the same film specimen. Force, puncture strength, energy at break, modulus, and strain were investigated as a function of water exposure time with respect to the type of polymer and the type and concentration of plasticizer and pore former (hydroxypropyl methylcellulose, HPMC). Eudragit RS films were very flexible, had a high strain, and broke upon puncture with only small cracks. In contrast, ethylcellulose films were more brittle with a lower strain and showed complete film rupture. Increased amounts of the hydrophilic pore former, HPMC, resulted in a reduced puncture strength and in an increase in water uptake and weight loss of the films. The puncture strength decreased with increasing plasticizer concentration and was lower with the lipophilic dibutyl sebacate than with the hydrophilic triethyl citrate.

Topics: Acrylic Resins; Cellulose; Citrates; Dicarboxylic Acids; Drug Delivery Systems; Hypromellose Derivatives; Mechanics; Methylcellulose; Pulsatile Flow; Time Factors; Water

The objective of the present study was to develop once-daily sustained-release matrix tablets of nicorandil, a novel potassium channel opener used in cardiovascular diseases. The tablets were prepared by the wet granulation method. Ethanolic solutions of ethylcellulose (EC), Eudragit RL-100, Eudragit RS-100, and polyvinylpyrrolidone were used as granulating agents along with hydrophilic matrix materials like hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose, and sodium alginate. The granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, and in vitro release studies. The granules showed satisfactory flow properties, compressibility, and drug content. All the tablet formulations showed acceptable pharmacotechnical properties and complied with in-house specifications for tested parameters. According to the theoretical release profile calculation, a once-daily sustained-release formulation should release 5.92 mg of nicorandil in 1 hour, like conventional tablets, and 3.21 mg per hour up to 24 hours. The results of dissolution studies indicated that formulation F-I (drug-to-HPMC, 1:4; ethanol as granulating agent) could extend the drug release up to 24 hours. In the further formulation development process, F-IX (drug-to-HPMC, 1:4; EC 4% wt/vol as granulating agent), the most successful formulation of the study, exhibited satisfactory drug release in the initial hours, and the total release pattern was very close to the theoretical release profile. All the formulations (except F-IX) exhibited diffusion-dominated drug release. The mechanism of drug release from F-IX was diffusion coupled with erosion.

Topics: Antihypertensive Agents; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Compounding; Hypromellose Derivatives; Methylcellulose; Nicorandil; Tablets

The purpose of this study was to develop a new method for preparing controlled release (CR) matrix pellets by annealing with water-insoluble polymers, and to elucidate a relationship between the annealing temperature of the matrix pellets and a glass transition temperature (T(g)) or a minimum film-forming temperature (MFT) of the polymer/plasticizer systems that constituted the matrix pellets. The pellets containing theophylline as a model drug were prepared by the extrusion-spheronization method and subsequent annealing. The pellets were characterized mainly by pellet formation, release studies, and thermal evaluations. It was apparent that the annealing temperature for the CR matrix pellets was related to the T(g) and MFT of the polymer/plasticizer systems. For ethylcellulose (EC) containing 22.7% triethylcitrate (TEC), the annealing temperature required for preparing CR pellets was 80 degrees C, which was more than 20 degrees C higher than the T(g) and MFT of this EC/TEC system. In contrast, hydroxypropylmethylcellulose acetate succinate (HPMCAS) containing 22.7% TEC could be used to prepare CR pellets without heating. The T(g) of this HPMCAS/TEC system was about 60 degrees C and the MFT was lower than 20 degrees C, indicating that water can act as a plasticizer for HPMCAS and that HPMCAS/TEC pellets could be annealed at room temperature. These results suggest that MFT is a better indicator than T(g) for estimating annealing temperature. SEM observation showed that the EC/TEC pellets annealed at 80 degrees C had a matrix structure with coalesced particles. On the contrary, unannealed pellets consisted of individually distinguishable particles. The release rate of drug from the matrix CR pellets was dependent on the drug concentration and polymer to plasticizer ratio.

Topics: Cellulose; Drug Compounding; Drug Implants; Drug Stability; Excipients; Hardness; Methylcellulose; Microscopy, Electron, Scanning; Particle Size; Polymers; Solubility; Temperature; Theophylline; Water; X-Ray Diffraction

4-Aminosalicylic acid has the potential for use in the treatment of diseases of the colon.. To assess the feasibility of delivering 4-aminosalicylic acid directly to the colon using a hydroxypropylmethylcellulose capsule coated with a mixture of amylose, a polysaccharide metabolized by bacterial enzymes in the colon, and ethylcellulose.. Seven healthy male volunteers received, on three separate occasions, an uncoated or amylose-ethylcellulose-coated hydroxypropylmethylcellulose capsule containing 4-aminosalicylic acid Na (550 mg), or an intravenous injection of 4-aminosalicylic acid Na (135 mg). The capsules were radiolabelled with 99mTc to allow their positions in the gastrointestinal tract to be followed using a gamma camera. Plasma and urine samples were collected and assayed for 4-aminosalicylic acid and metabolite concentrations.. The uncoated capsules broke down within 10 min in the stomach, allowing rapid and complete absorption of the drug. The coated capsules remained intact in the upper gastrointestinal tract, and had a median gastric emptying time of 61 min (interquartile range, 77 min) and a median colon arrival time of 363 min (interquartile range, 185 min). For the coated capsules, only the metabolite was detected in the plasma and/or urine after the capsules had reached the colon.. The specific coating protected the drug until the capsule reached the colon, where 4-aminosalicylic acid was slowly released and absorbed. Thus, such a formulation has the potential for use in the treatment of inflammatory bowel disease.

Topics: Adult; Aminosalicylic Acid; Amylose; Capsules; Cellulose; Chemistry, Pharmaceutical; Colon; Delayed-Action Preparations; Digestive System; Feasibility Studies; Gastrointestinal Agents; Humans; Hypromellose Derivatives; Injections, Intravenous; Male; Methylcellulose; Radionuclide Imaging; Technetium

The objective of this study was to compare the performance of cellulose acetate (CA) and ethylcellulose (EC)-HPMC combination coatings as semipermeable membranes (SPMs) for osmotic pump tablets (OPTs) of naproxen sodium (NPS) so as to deliver a constant, predetermined amount of drug in solution form over a fixed span of time, independent of external environmental conditions. Osmotic pump tablets were designed with different coating variables and optimized in terms of nature of plasticizer, membrane thickness, and orifice diameter. The effect of insertion of an inner microporous film around the NPS core to minimize deformation of the SPM due to peristaltic movement of the gut was also studied. Osmotic pump tablets composed of membranes with water-soluble plasticizer, propyleneglycol (PG), released drug mainly through diffusion, whereas those designed with CA and EC-HPMC (4:1) coats containing water-insoluble plasticizer, castor oil, released their contents by perfect zero-order kinetics over a prolonged period of time, though the average release rate that could be achieved with the EC-HPMC (4:1) membrane was only about half the rate achieved with the CA membrane for the same membrane thickness. Release rates for both the membranes decreased with increasing membrane thickness and were found to be independent of orifice diameter, agitation intensity, and pH of the dissolution medium.

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Dosage Forms; Drug Compounding; Excipients; Hypromellose Derivatives; Methylcellulose; Naproxen; Osmosis; Permeability; Tablets

A new method for preparation of large amounts of empty pressure-controlled colon delivery capsules (PCDCs) by a dipping method has been developed. Empty PCDCs are composed of two polymer membranes. The inner one was a water-insoluble polymer membrane, ethylcellulose (EC). The outer one was an enteric polymer membrane, hydroxypropylmethylcellulose phthalate (HPMCP) or hydroxypropylmethylcellulose acetate succinate (HPMCAS). By consequently dipping into an ethanolic EC solution and an alkalized enteric polymer solution, empty PCDCs were obtained after both the capsule body and cap were adjusted to the size of #2 capsules. With each enteric polymer, two types of empty PCDCs of different thickness were prepared. Fluorescein (FL) was formulated with suppository base, PEG1000, and used as a model drug. FL/PEG1000 suspension was introduced into empty PCDCs which were then sealed with enteric polymer solution. The PCDCs were evaluated by an in vivo experiment using beagle dogs. After oral administration of the test PCDC preparations containing 30 mg of FL, blood samples were obtained from the jugular vein and serum FL levels were measured. The thickness of the EC membrane layer varied in both the capsule body and cap. HPMCAS PCDCs had 62.1+/-5.0 (S.E.) microm (body) and 49.7+/-3.3 microm (cap) with thicker ones and 55.7+/-6.6 microm (body) and 46.8+/-6.2 microm (cap) with thinner ones. HPMCP PCDCs had 28.1+/-3.3 microm (body), 30.9+/-1.0 microm (cap) with thinner ones and 43.1+/-9.8 microm (body), 42.4+/-8.2 microm (cap) with thicker ones. The mean T(i) values, the first appearance time, of FL in the serum of HPMCAS PCDCs were 2.0+/-0.7 h for thicker ones and 3.8+/-0.5 h for thinner ones, while the mean T(i) values of HPMCP PCDCs were 2.0+/-0.0 h for thinner ones and 3.5+/-0.7 h for thicker ones. Since the colon arrival time in beagle dogs was 3.5+/-0.3 h as determined by a sulfasalazine test, thinner HPMCAS PCDCs and thicker HPMCP PCDCs were thought to deliver FL to the colon.

Topics: Animals; Area Under Curve; Capsules; Cellulose; Colon; Contrast Media; Dogs; Drug Delivery Systems; Excipients; Fluorescein; Male; Methylcellulose; Sclerosing Solutions

The release of metoclopramide hydrochloride (a very water soluble cationic drug) and diclofenac sodium (a sparingly soluble anionic drug) from pellets coated with Surelease containing hydroxypropylmethylcellulose (HPMC) at different coating loads was investigated. The release rates of either drug at each coating composition decreased as the coating load increased. Inclusion of HPMC E15 increased the release rates of both drugs compared to pellets coated only with Surelease. This was thought to be due to the leakage of the soluble part of the film (HPMC E15) during dissolution, which left pores for drug release. The Surelease:HPMC E15 ratio had a major role in the release rates of drugs. Addition of HPMC E15 into Surelease did not change the release mechanism for metoclopramide hydrochloride (the mean value of n approximately 0.57) from that of Surelease alone, and diffusion remained the main mechanism controlling the release. However, the release exponent (approximately 1.28) increased for diclofenac sodium on addition of HPMC E15, indicating a dissolution-controlled mechanism. Despite its lower water solubility, diclofenac sodium was released slightly faster than metoclopramide hydrochloride from pellets coated with Surelease containing HPMC E15 at equivalent coating loads.

Topics: Algorithms; Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Delayed-Action Preparations; Diclofenac; Dopamine Antagonists; Drug Delivery Systems; Drug Design; Lactose; Methylcellulose; Metoclopramide; Oxazines; Permeability; Sclerosing Solutions

The aim of this study was to relate the color of several binary mixes to their organization as observed by scanning electronic microscopy, and to their compactibility. Binary mixes of niflumic acid (yellow) with ethyl cellulose, hydroxypropylmethylcellulose, low-substituted hydroxypropylcellulose (L-HPC), and ibuprofen (all white) were prepared using different particle size ranges. Colors of the mixes were determined by diffuse reflectance spectroscopy using a chromameter. Linear correlation was observed between the yellowness index/whiteness index ratio (Y/W ratio) defined by the American Society for Testing and Materials (ASTM) standards and the mean particle size difference of the materials which governs the organization of the blend. Except for the least interacting mix, the niflumic acid/L-HPC series, the color of the blend was also related to the tensile strength of the tablets made from the binary mixes. Color could be an interesting indicator of the organization of a powder mix. Diffuse reflectance spectroscopy could be used as a quality control tool because any modification of the color of the mix may be an indicator of a modification of its compactibility.

Topics: Cellulose; Color; Colorimetry; Ibuprofen; Lactose; Methylcellulose; Microscopy, Electron, Scanning; Niflumic Acid; Oxazines; Particle Size; Powders; Spectrum Analysis; Surface Properties; Tablets; Tensile Strength

The mechanical and rheologic properties of wet masses of pharmaceutical powders determine their processibility and the quality of the product prepared by extrusion/spheronization. In this work, a triaxial compression test was attempted for the first time to characterize material properties of pharmaceutical wet masses of different hydrophilicity and particle sizes. The stress-strain curves and the pore pressure were determined at various cell pressures. The failure criteria of the wet masses were obtained from the stress path on the deviator stress plane. The cohesion (c) and the angle of internal friction (phi) were evaluated from the intercept and the slope of the failure loci. The stress-strain behavior strongly depended on the type of powders and cell pressure. The values of c and phi were similar for wet masses of EC FP, MCC PH101, and SMCC 50, but a very small phi and a very high c value for HPMC. The shear strength and rigidity of the wet masses were in the order of EC FP > SMCC 50 > MCC PH101 > HPMC, whereas the elastic recovery was in the opposite order. These material parameters could be used as references for selection of excipients and formulation for extrusion/spheronization.

Topics: Cellulose; Compressive Strength; Excipients; Hypromellose Derivatives; Methylcellulose; Particle Size; Powders; Rheology; Water

The release of metoclopramide hydrochloride (very water soluble cationic drug) and diclofenac sodium (sparingly soluble anionic drug) from pellets coated with hydroxypropylmethylcellulose (HPMC; water-soluble polymer) or ethylcellulose aqueous dispersion (Surelease; water-insoluble polymer) at different coating loads was investigated. The release rates of either drug decreased as the coating load of HPMC increased, but overall, the release was fast, and the majority of both drugs released in about 1 hr, even at the highest coating load. The drug release mechanism for either drug was not affected by the coating load of HPMC or by the type of drug used, and it was found to be mainly diffusion controlled. Diclofenac sodium released slightly more slowly than metoclopramide hydrochloride from HPMC-coated pellets. This was attributed to the lower water solubility of the former drug. The release rate of either drug decreased greatly as the coating load of Surelease increased. The release of both drugs was sustained over 12 hr as the coating load of Surelease increased, and only about 70% of either drug was released after this period at the highest coating load (20%). The mechanism of release of metoclopramide hydrochloride was independent of coating load, and it was predominantly diffusion controlled. However, the mechanism of diclofenac sodium release was dependent on the coating load of Surelease. At low coating loads, diffusion of drug was facilitated due to the presence of more pores at the surface of the coated pellets; therefore, the rate of dissolution of the drug particles was the rate-limiting step. However, at high coating loads, drug release was mainly diffusion controlled. Despite its lower water solubility, diclofenac sodium released slightly faster than metoclopramide hydrochloride from Surelease-coated pellets at equivalent coating loads.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diclofenac; Drug Compounding; Lactose; Methylcellulose; Oxazines; Solubility; Water

The present work investigates release mechanisms of theophylline pellets coated with an aqueous ethyl cellulose (EC) dispersion containing plasticizers and hydroxypropyl methylcellulose (HPMC) as a water soluble pore former. Three different drug release mechanisms from coated pellets can be determined as a function of the water solubility of the plasticizers and the ionic strength of the release medium. Coated pellets with the addition of more hydrophilic plasticizers such as triethyl citrate (TEC) or diethyl phthalate (DEP) show an approximate zero-order-release rate. In contrast, two-phase release profiles can be observed from pellets coated with dispersions containing hardly soluble plasticizers such as dibutyl phthalate (DBP) or dibutyl sebacate (DBS). Only in a release medium of high ionic strength the water soluble pore former will remain in the coating. Thus the drug diffuses through a hydrated swollen membrane containing EC, HPMC and insoluble plasticizer. The release mechanisms depend on the glass transition temperature of the ethyl cellulose and therefore on the migration of the plasticizers and the pore former. This was shown by investigation of the migration of the additives and the influence of the temperature of the release medium on the release. Additionally, the study investigates the effect of curing and storage conditions of coated pellets on the drug release rate.

Topics: Cellulose; Drug Implants; Lactose; Methylcellulose; Osmolar Concentration; Oxazines; Plasticizers; Solubility; Tablets, Enteric-Coated; Temperature; Theophylline; Water

Elucidate the compactibility of binary mixes from their organization as compared to the traditional approach involving the different behavior of the materials under compression (plastic or brittle).. Several materials were selected from their surface energies. Binary mixes 50/50 v/v were prepared from different sieved or freeze-milled fractions. The tensile strengths of the tablets obtained at two compression forces were compared with those of series of compacted binary mixes containing different proportions of the raw materials (concept of equivalent media).. In the case of interacting mixes, when the differences in particle size between the fractions blended increased, the material with the lowest particle size coated the largest particles more efficiently. Consequently, the tensile strengths of the tablets obtained became closer to the tensile strengths obtained from the pure coating material. For the non-interacting systems, the experimental tensile strengths were very close to the values calculated from the tensile strengths of the pure materials.. This study clearly demonstrates the influence of the organization of binary mixes on their compactibility. The adhering material makes a percolating network governing the tensile strength of the tablet. From an industrial point of view, it is possible to improve the compactibility of binary mixes without changing their composition by selecting the appropriate organization.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticholesteremic Agents; Cellulose; Drug Compounding; Drug Delivery Systems; Hypromellose Derivatives; Methylcellulose; Microscopy, Electron, Scanning; Niflumic Acid; Particle Size; Powders; Surface Properties; Tablets; Tensile Strength

Usually, chemical or technological operations are used to mask the taste of unpleasant-tasting drugs. To reduce the development cost of such drugs, we propose a new approach which does not require the modification of the existing formulation nor the use of additional costly technological operations. Different particle size fractions of two unpleasant-tasting drugs (niflumic acid and ibuprofen) were blended in binary mixes with different particle size fractions of two non-tasting excipients (ethyl cellulose and hydroxypropyl methylcellulose). By selecting the appropriate mixes of identical composition but different organisations, as predicted from surface energy data, it was possible to use the different organisations to modify the taste of the mixes for a panel of 10 healthy volunteers.

Topics: Adolescent; Adult; Cellulose; Chemistry, Pharmaceutical; Female; Humans; Hypromellose Derivatives; Ibuprofen; Male; Methylcellulose; Niflumic Acid; Particle Size; Powders; Taste; Technology, Pharmaceutical

The aim of this study was to relate the organization of several binary mixes with three physical parameters (surface energy, cohesion parameter, and particle size) of various materials blended with each other.. Four pharmaceutical compounds were selected for their surface energies and cohesion parameters. Binary mixes were prepared from different sieved fractions. The frequency and nature of the interactions between the particles were observed by scanning electron microscopy.. As expected, interactions were determined by both the energetics and the relative particle size of the two compounds blended, the latter determining the mode of interaction. However, particle size was not the only factor influencing the organization of the blends as, sometimes, small particles of a material would not adhere to the coarser particles of the other. Thus, a surface energy derived parameter ¿(B/A)lambda - (A/B)lambda¿ appears to be a valuable estimating tool of the potentiality of interaction between the particles blended. No correlation between the cohesion parameters of the compounds and the organization of the resulting blends could be found.. Surface energy and particle size play a major role in the organization of a binary blend. However, they cannot explain separately the interactions observed between the fractions blended as reliable predictions require the use of both characteristics.

Topics: Adhesiveness; Cellulose; Energy Transfer; Hypromellose Derivatives; Ibuprofen; Linear Models; Methylcellulose; Microscopy, Electron, Scanning; Models, Molecular; Niflumic Acid; Particle Size; Solubility; Surface Properties

This investigation was carried out to try the application of pilocarpine hydrochloride (PC) solid dispersion as sustained release dosage form. Four preparations of PC with ethylcellulose and/or hydroxypropylmethylcellulose phthalate were prepared by the organic solvent method. The preparation D including PC: ethylcellulose: hydroxypropylmethylcellulose phthalate (1:9:10 at weight ratio) showed the best sustained release behavior in dissolution test among four preparations. The preparation D was examined by powder X-ray diffractometry and differential scanning calorimetry, and confirmed to be solid dispersion. Saliva secretory effect of preparation D was examined in healthy male volunteers, and its effect for Xerostomia was showed.

Topics: Cellulose; Delayed-Action Preparations; Dosage Forms; Humans; Hypromellose Derivatives; Male; Methylcellulose; Pilocarpine; Saliva; Stimulation, Chemical; Xerostomia

The purpose of this study was to investigate the potential of near-infrared (near-IR) spectroscopy for non-destructive at-line determination of the amount of polymer coat applied to tablet cores in a Wurster column.. The effects of coating composition on the near-IR spectroscopic determination of ethylcellulose (Aquacoat ECD-30) or hydroxypropylmethylcellulose (HPMC)-based (Spectrablend) coating were evaluated, as were the performance of several chemometric techniques.. Tablets were coated with up to 30% ethylcellulose or 22% HPMC, and samples were pulled at regular intervals during each coating run. Near-IR reflectance spectra of the intact tablets were then collected. The spectra were preprocessed by multiplicative scatter correction (MSC) or second derivative (D2) calculations, and calibrations developed using either principal components (PCs) or multiple spectral wavelengths. The near-IR method provided predictions of film applied with standard errors of 1.07% w/w or less.. Near-IR spectroscopy can be profitably employed in a rapid and non-destructive determination of the amount of polymer film applied to tablets, and offers a simple means to monitor the film coating process.

Topics: Calibration; Cellulose; Chemistry, Pharmaceutical; Evaluation Studies as Topic; Lactose; Methylcellulose; Oxazines; Spectrophotometry, Infrared; Tablets

A spray method for the preparation of free films from aqueous polymeric dispersions was investigated. Free films were prepared from aqueous dispersions of methacrylic acid-ethyl methacrylate copolymer (Eudragit L 30D), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cellulose acetate phthalate (CAP), and ethyl cellulose (EC) by a spray method and a cast method, and their mechanical properties and reproducibility were investigated. Uniform films were obtained from the dispersions of Eudragit L 30D, HPMCAS, and EC by the spray method, but films could not be formed by spraying the CAP dispersion. The tensile strength, elongation, and elastic modulus of the sprayed Eudragit L 30D films were similar to the properties of the cast films, and good reproducibility was obtained from both methods. Marked within-run variation in the mechanical properties was observed for the cast HPMCAS and CAP films, which could be due to a settling of the solid particles during the drying step. The variation in the mechanical properties of the sprayed HPMCAS films was lower and the tensile strength significantly higher than that of the cast films. There were also significant differences in tensile strength and elongation of EC films between products of the two methods. The results indicated that the spray method used to prepare the free films from aqueous polymeric dispersions provided uniform films with consistent and reproducible properties.

Topics: Acrylic Resins; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dosage Forms; Gels; Methylcellulose; Polymers; Polymethacrylic Acids; Reproducibility of Results; Surface Properties; Water

A new oral controlled-release drug delivery system was developed with two polymers using a multiple-emulsification technique. Powdered drug was dispersed in methyl cellulose sol, which was emulsified in ethyl cellulose solution in ethyl acetate. The primary emulsion thus formed was reemulsified in aqueous medium. During this phase, discrete microspheres were formed under optimized conditions. The size distribution of the microspheres was investigated, and scanning electron microscopy revealed the surface topography of the microspheres. The in vitro drug release followed first-order diffusion-controlled dissolution. More than 85% of the drug was released over 6 hr at pH 6.2 for all dissolution batches.

Topics: Administration, Oral; Cellulose; Delayed-Action Preparations; Drug Delivery Systems; Indomethacin; Methylcellulose; Microscopy, Electron, Scanning; Microspheres; Solubility

Hydroxy propyl methyl cellulose acetate succinate high grade (AS-HG) and ethyl cellulose (EC) mixture microcapsules containing cefadroxil or theophylline were prepared by a solvent evaporation method in liquid paraffin dissolved sorbitan tri-stearate as a dispersing agent, and their sustained-release properties were evaluated. The microcapsules prepared with AS-HG:EC (in a 2:5 weight ratio) mixture containing 20% of cefadroxil or theophylline exhibited apparent zero-order releasing pattern in pH 6 to 8, at 50 rpm and 37 degrees C (paddle method). These microcapsules were administered orally to beagle dogs and the plasma concentrations of cefadroxil or theophylline were measured periodically. As a result of in vivo investigation, a satisfactory sustained-release plasma pattern and an apparent zero-order process in the gastrointestinal absorption were confirmed by deconvolution analysis of both drugs.

Topics: Administration, Oral; Animals; Cefadroxil; Cellulose; Delayed-Action Preparations; Dogs; Drug Compounding; Intestinal Absorption; Male; Methylcellulose; Theophylline

The effects of physical aging on the water permeation of cellulose acetate and ethylcellulose, the mechanical properties of ethylcellulose, and the dissolution property of hydroxypropyl methylcellulose phthalate were investigated. The water permeabilities of cellulose acetate and ethylcellulose and the dissolution rate of hydroxypropyl methylcellulose phthalate were found to decrease with physical aging time after being quenched from above the glass transition temperatures to sub-Tg temperatures. The gradual approach toward thermodynamic equilibrium during physical aging decreases the free volume of the polymers. This decrease in free volume is accompanied by a decrease in the transport mobility, with concomitant changes in those properties of the polymer that depend on it. The effects of long-term aging on the dissolution rate and water permeabilities of these polymers can be estimated from a linear double-logarithmic relationship between the mobility properties and physical aging time. The existence of the linear double-logarithmic relationship can be derived from the Williams-Landel-Ferry equation, the Doolittle equation, Struik's model, and Fujita's relationship between diffusion and free volume.

Topics: Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Methylcellulose; Permeability; Polymers; Solubility; Tablets; Temperature; Time Factors

To modify the release rate of piretanide, a potent loop diuretic, a double-layer tablet was designed, and in vitro release was evaluated. For a rapidly releasing portion, hydrophilic beta-cyclodextrin derivatives were employed to form a water-soluble complex with piretanide. For a sustained-release portion, cellulose derivatives were used to provide appropriate hydrophobicity. The release rate of piretanide in the pH range 1.2-6.8 was automatically monitored by a pH-changeable dissolution testing apparatus. The low solubility of piretanide in acidic medium was significantly improved by complexations with dimethyl-beta-cyclodextrin (DM-beta-CyD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CyD). The pH-independent slow release was attained by use of hydroxypropylcellulose (HPC):ethylcellulose (EC) matrices. Then, an optimal formulation of a double-layer tablet was obtained by the combination of each fraction. For example, the tablet consisting of the [DM-beta-CyD/(HPC:EC)] system in the weight ratio [1/3(1:3)] provided a sufficiently slow release of the drug over a period of 8 h in a wide pH region following an initial rapid dissolution.

Topics: beta-Cyclodextrins; Cellulose; Chemistry, Pharmaceutical; Crystallization; Cyclodextrins; Delayed-Action Preparations; Drug Carriers; Hydrogen-Ion Concentration; Hypromellose Derivatives; Methylcellulose; Solubility; Sulfonamides; Tablets; X-Ray Diffraction

A method is described for the analysis of positions of substitution of O-methyl and O-ethyl groups in commercial samples of O-methylcellulose and O-ethylcellulose, respectively. The method requires perethylation of O-methyl-cellulose and permethylation of O-ethylcellulose. Subsequent reductive cleavage of both polymers gives the same eight products, which are analyzed as their O-acetyl derivatives by gas-liquid chromatography.

Topics: Alkylation; Cellulose; Chromatography, Gas; Hydrolysis; Indicators and Reagents; Methylation; Methylcellulose; Oxidation-Reduction

Typical two dimensional solubility parameter maps for ethyl cellulose, hydroxypropyl methylcellulose and hydroxypropyl cellulose have been constructed using literature data. The maps of the polymers showed some degree of overlap indicating some mutual compatibility. Compatibility between ethyl cellulose and hydroxypropyl cellulose was greater than between ethyl cellulose and hydroxypropyl methylcellulose. The maps may also be used to predict the effect of added plasticizers.

Topics: Cellulose; Chemistry, Pharmaceutical; Drug Incompatibility; Hypromellose Derivatives; Methylcellulose; Plasticizers; Solubility

The experiences from a total of 303 small intestine examinations of different techniques show that especially the double-contrast representation using barium sulfate and air achieves the best diagnostical findings. The double-contrast representation can be achieved by an antegrade small intestine enema (enteroclysis) or within the conventional small intestine passage by retrograde air insufflation. These examination techniques make optimal fine diagnostics especially of the lower ileum possible. The indications for the different methods are explained.

Topics: Air; Barium Sulfate; Cellulose; Contrast Media; Crohn Disease; Diverticulum; Enema; Humans; Intestinal Diseases; Intestine, Small; Methylcellulose; Radiography; Tissue Adhesions; Water