methylcellulose and carboxypolymethylene

An ointment base for better treatment of bedsores was developed to improve the release rate of minocycline hydrochloride (MH) and the water absorption capacity using various types of hydrophobic to hydrophilic ointment bases. The effect of purified lanolin (PL) on the release behavior of MH from a hydrophilic ointment (HO) base was the primary focus. It was found that the drug release rate from the ointment base was modified according to the method of preparation of the ointment base and the type of cyclodextrins admixed. The physicochemical properties, such as viscosity, elution volume, and water absorption, of the ointment base were also modified by those factors. To develop an ointment formulation suitable for the recovery stages of bedsores, including the proliferation period of granulation and the formative period of epidermis, the physicochemical properties of Macrogol ointment containing various hydrophilic polymers, which have gel-forming ability, were tested. A novel ointment base suitable for the treatment in the recovery stage of bedsores was developed using hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC). Considerably sustained release of MH (T50 of 170 at a min) was attained with a macrogol ointment mixed with HM-HPMC and Carbopol formulation ratio of 3:7. We clinically evaluated the effectiveness of bedsore treatment by applying different ointment bases to patients with different stages of bedsores.

Topics: Absorption; Acrylic Resins; Chemical Phenomena; Chemistry, Pharmaceutical; Chemistry, Physical; Controlled Clinical Trials as Topic; Cyclodextrins; Delayed-Action Preparations; Drug Design; Gels; Humans; Hypromellose Derivatives; Lanolin; Methylcellulose; Minocycline; Ointment Bases; Ointments; Polyethylene Glycols; Polyvinyls; Pressure Ulcer; Severity of Illness Index; Water

A novel ointment base suitable for the treatment of bedsore at the recovery stage was developed by the use of hydroxypropyl methylcellulose (HM-HPMC) modified on the basis of the hydrophobicity. A considerable sustained release of drug (minocycline hydrochloride) formulated to the ointment (T50 of 170 min) was attained with a macrogol ointment (MO) mixed with the HM-HPMC and Carbopol (CP) of the formulating ratio of 3:7. It was also found that a change in the formulating ratio of HM-HPMC and CP lead to a change in the drug release rate. The water absorption property of the ointment base, required to absorb on exudative solution in applying to the bedsore treatment, was as high as that of an ointment base containing hydroxypropyl cellulose (HPC) and CP reported in our previous paper. We clinically evaluated the effectiveness of the bedsore treatment, in which different ointment bases were applied to patients at different stages of the bedsore. A total of 22 cases were divided into two categories for applying to the different treatments. One category comprised of 11 subjects was treated with a povidone-iodine sugargel, which was the conventional method in our hospital, while the other 11 subjects were treated by the use of the newly developed ointment bases in consideration for the different stages of the bedsore. In comparison of the clinical results with the healing index, we ascertained that the latter method was significantly more efficacious (p < 0.01-0.05) than the conventional one. The effectiveness was emphasized in treating the intractable bedsore classified into the grades IV and V. Therefore, we confirmed that the newly developed ointment base formulation is useful in treating bedsore at each stage.

Topics: Acrylic Resins; Aged; Chemical Phenomena; Chemistry, Physical; Female; Gels; Humans; Hypromellose Derivatives; Male; Methylcellulose; Middle Aged; Minocycline; Ointment Bases; Ointments; Polyvinyls; Pressure Ulcer; Severity of Illness Index; Treatment Outcome

Systemic absorption of ocularly administered Brimonidine Tartrate has been reported to give rise to several side-effects. Hence, it has become crucial to develop a delivery system that could increase efficacy and reduce systemic absorption. Therefore, the present work aims to develop Brimonidine Tartrate gels with different concentrations (0.05%, 0.1%, and 0.2% w/v, respectively) using Carbopol 974 P and HPMC E4M, and compare the therapeutic efficacy and systemic absorption with that of eye drop (0.2%, w/v) by UPLC-MS/MS. The result of histological analysis did not show any morphological or structural changes after the administration of formulations. In vitro residence time studies demonstrated that the gels exhibited a better precorneal residence time as compared with the eye drop. The gels with lower concentrations of the drug (0.05% and 0.1%, w/v) could significantly decrease intraocular pressure (IOP) in both normal and water-loaded rabbits as compared to the eye drop. Finally, the values of the ratio of AUC

Topics: Absorption, Physiological; Acrylic Resins; Administration, Ophthalmic; Animals; Biological Availability; Brimonidine Tartrate; Gels; Intraocular Pressure; Lactose; Methylcellulose; Ophthalmic Solutions; Rabbits

Ciprofloxacin (CIP) is a poorly soluble drug that also displays poor permeability. Attempts to improve the solubility of this drug to date have largely focused on the formation of crystalline salts and metal complexes. The aim of this study was to prepare amorphous solid dispersions (ASDs) by ball milling CIP with various polymers. Following examination of their solid state characteristics and physical stability, the solubility advantage of these ASDs was studied, and their permeability was investigated via parallel artificial membrane permeability assay (PAMPA). Finally, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the ASDs were compared to those of CIP. It was discovered that acidic polymers, such as Eudragit L100, Eudragit L100-55, Carbopol, and HPMCAS, were necessary for the amorphization of CIP. In each case, the positively charged secondary amine of CIP was found to interact with carboxylate groups in the polymers, forming amorphous polymeric drug salts. Although the ASDs began to crystallize within days under accelerated stability conditions, they remained fully X-ray amorphous following exposure to 90% RH at 25 °C, and demonstrated higher than predicted glass transition temperatures. The solubility of CIP in water and simulated intestinal fluid was also increased by all of the ASDs studied. Unlike a number of other solubility enhancing formulations, the ASDs did not decrease the permeability of the drug. Similarly, no decrease in antibiotic efficacy was observed, and significant improvements in the MIC and MBC of CIP were obtained with ASDs containing HPMCAS-LG and HPMCAS-MG. Therefore, ASDs may be a viable alternative for formulating CIP with improved solubility, bioavailability, and antimicrobial activity.

Topics: Acrylic Resins; Ciprofloxacin; Methylcellulose; Microbial Sensitivity Tests; Polymers; Polymethacrylic Acids; Solubility

This study focuses on the development of amlodipine bilayer buccal tablets of hydroxypropyl methylcellulose (HPMC) matrix system containing polyacrylate polymer (Carbopol(®))/β-cyclodextrin as the drug layer and ethylcellulose as the non-swellable backing layer, and their biointerfacial phenomena.. Tablets were evaluated for swelling, erosion and mucoadhesion using buccal mucosal tissue ex vivo. In vitro drug release and ex vivo drug transport across mucosal tissue were also performed in phosphate buffer (pH 6.8). The relationship of swelling with buccoadhesion and buccal permeation of various bilayer tablet formulations containing HPMC alone and in combination with Carbopol or drug-β-cyclodextrin complex has been prepared.. Overall buccoadhesion of the tablet with combination of HPMC and Carbopol was increased significantly compared with that of HPMC alone. Presence of cyclodextrin did not change bioadhesion force and swelling behavior significantly. Ex vivo permeation was increased with the increase of HPMC proportion in other formulations as observed in in vitro dissolution.. Drug-cyclodextrin complexes in the tablet improved permeation due to its improved dissolution at the site of biointerface of tablet and buccomucosa. Correlations of ex vivo and in vitro data have been established to predict the buccomucosal permeation from the swelling index or drug release alone.

Topics: Acrylic Resins; Administration, Buccal; Amlodipine; Animals; beta-Cyclodextrins; Biological Transport; Calcium Channel Blockers; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Drug Delivery Systems; Lactose; Male; Methylcellulose; Mouth Mucosa; Sheep; Spectroscopy, Fourier Transform Infrared; Tablets

PL cream (combination of lidocaine and procaine) was launched on the market in April 2012 in Japan. We investigated differences in the anesthetic effect by employing two types of base: Carbopol and methylcellulose. Electron microscopy showed a distinct difference in appearance: densely-scattered, fine particles for Carbopol and sparse, large particles for methylcellulose. Accordingly, the extensibility of the cream was significantly greater at 4 and 25 degrees centigrade for methylcellulose, but was greater at 34 degrees centigrade for Carbopol. The steady flow viscosity (1 s(-1)) was greater for the Carbopol than methylcellulose base. The difference in the cutaneous permeability between the two bases increased over time: the methylcellulose base was removed at 90 min after application and, 30 min later, showed a significant difference. These results suggest that the methylcellulose base has a superior anesthetic effect in clinical settings.

Topics: Acrylic Resins; Administration, Topical; Anesthetics, Local; Animals; Chemistry, Pharmaceutical; Female; Humans; In Vitro Techniques; Lidocaine; Male; Methylcellulose; Mice; Mice, Nude; Ointment Bases; Pain; Permeability; Skin; Viscosity

This study was to optimize HPMC K4M and carbopol 934 concentration in the development of non-effervescent floating tablets (NEFTs) of glipizide as model drug using 3(2) factorial design. The time required for releasing drug of 50% and 80% and similarity factor were the target responses. HPMC K4M and carbopol 934 concentrations were the variables. The response surface methodology and optimized polynomial equations were used to select the optimal formulation with desired responses. The excipients used in tablets were compatible with glipizide as per the results of isothermal stress testing and DSC study. The drug release of entire NEFTs followed zero order kinetics and non-Fickian diffusion mechanism. Validation of the optimization technique demonstrated the reliability of the model. The optimized formulation containing 124.33 mg HPMC K4M and 25.76 mg carbopol 934 was prepared according to the software determined levels. The stability study of the optimized formulation proved the integrity of the developed formulation.

Topics: Acrylic Resins; Calorimetry, Differential Scanning; Hypromellose Derivatives; Materials Testing; Methylcellulose; Pharmacokinetics; Tablets

To study the preparation of total flavones in Glechoma longituba sustained-release tablets and evaluate its releasing features in vitro.. Orthogonal experiment (L(9)3(4)) was used to optimize the process of preparation of total flavones in Glechoma longituba sustained-release tablets. Investigated the release effect in vitro of optimization test result.. The optimized prescription was HPMC-K4M and carbopol 934p account for 30% of the total tablet weight, their dosage ratio was 2: 1; Lactose as additives, 20% dosage; 5% PVP ethanol as adhesives, and compressed the wet granule of the materials into the total flavones in Glechoma longituba sustained-release tablets. The released profiles of the sustained-release tablets followed zero-order equation.. The sustained-release effect of total flavones in Glechoma longituba sustained-release tablets is good, the preparation craft is easy and feasible and worth widely promoting.

Topics: Acrylic Resins; Delayed-Action Preparations; Drug Stability; Ethanol; Excipients; Flavones; Lamiaceae; Methylcellulose; Polyvinyls; Reproducibility of Results; Solubility; Tablets; Technology, Pharmaceutical

A suitable topical formulation of mefenamic acid was developed in order to eliminate the gastrointestinal disorders associated with its oral administration. Drug coprecipitates prepared with different polymers at various drug-to-polymer ratios improved drug solubility and dissolution compared to pure drug and physical mixtures. PVP polymers (ratio 1:4) produced the best results. Aqueous ionic cream, ointments of absorption and water soluble bases and gels of methylcellulose, carboxymethylcellulose sodium, HPMC, Carbopol® 934 and 940, and Pluronic® F127 bases containing 1-10% drug as coprecipitates of PVP polymers (1:4) were prepared. The highest drug release was achieved at 1% drug concentration from water soluble base and methylcellulose among cream/ointment and gel bases, respectively. Gels, in general yielded better release than creams/ointments. All tested medicated creams/ointments exhibited plastic flow while all gels conformed to pseudoplasticity. Most of them showed thixotropy, a desired property of topical preparations. Stability studies revealed that HPMC and methylcellulose had the smallest changes in drug content, viscosity, and pH among the formulations. Considering drug release, rheological properties, and stability, methylcellulose gel containing 1% drug as coprecipitates of PVP K90 was the best among the studied formulations, was promising for improving bioavailability of mefenamic acid and can be used in future studies.

Topics: Absorption; Acrylic Resins; Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Drug Compounding; Drug Delivery Systems; Drug Stability; Gels; Humans; Mefenamic Acid; Methylcellulose; Ointment Bases; Ointments; Polyethylenes; Polypropylenes; Polyvinyls; Pyrrolidines; Rheology; Viscosity

We investigated how the Bradford assay for measurements of protein released from a drug formulation may be affected by a concomitant release of a pharmaceutical polymer used to formulate the protein delivery device. The main result is that polymer-caused perturbations of the Coomassie dye absorbance at the Bradford monitoring wavelength (595nm) can be identified and corrected by recording absorption spectra in the region of 350-850mm. The pharmaceutical polymers Carbopol and chitosan illustrate two potential types of perturbations in the Bradford assay, whereas the third polymer, hydroxypropylmethylcellulose (HPMC), acts as a nonperturbing control. Carbopol increases the apparent absorbance at 595nm because the polymer aggregates at the low pH of the Bradford protocol, causing a turbidity contribution that can be corrected quantitatively at 595nm by measuring the sample absorbance at 850nm outside the dye absorption band. Chitosan is a cationic polymer under Bradford conditions and interacts directly with the anionic Coomassie dye and perturbs its absorption spectrum, including 595nm. In this case, the Bradford method remains useful if the polymer concentration is known but should be used with caution in release studies where the polymer concentration may vary and needs to be measured independently.

Topics: Absorption; Acrylic Resins; Biochemistry; Chitosan; Hydrogen-Ion Concentration; Hypromellose Derivatives; Methylcellulose; Optical Phenomena; Ovalbumin; Polyvinyls; Rosaniline Dyes; Solutions; Spectrum Analysis

The purpose of the present research was to develop bioadhesive buccal tablets for Felodipine (FDP) and Pioglitazone (PIO), low bioavailability drugs, in a combined dosage form for the management of diabetes and hypertension. Buccal tablets were prepared by direct compression method using bioadhesive polymers hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, and carbopol, alone or in combination of two polymers, and were evaluated for physicochemical properties, swelling index, in vitro bioadhesion, in vivo residence time, in vitro drug release, and ex vivo permeation through porcine buccal membrane. Formulation (PF6) showed peak detachment force (3.12 N), work of adhesion (0.72 mJ), swelling index (196%), erosion (10.8%), in vivo residence time of 280 min, in vitro drug release (99.65% and 98.96% in 6 h for FDP and PIO, respectively) with higuchi model release profile and permeated 66.1 and 64.6 % with a flux of 0.118 and 0.331 mg/h/cm(2) of FDP and PIO through porcine buccal membrane. The bioavailability study for optimized formulation (PF6) in pigs showed 2.05- and 2.13-times statistically significant (p < 0.05) improvement in bioavailability for FDP and PIO, respectively, after administration of buccal tablets compared to oral suspension. The ex vivo-in vivo correlation was found to have a biphasic pattern and followed type A correlation. The stability of the PF6 was studied and no significant changes were detected in drug content and in vitro release and ex vivo permeation through porcine buccal membrane after 6 months.

Topics: Acrylic Resins; Adhesiveness; Administration, Buccal; Adult; Animals; Antihypertensive Agents; Biological Availability; Carboxymethylcellulose Sodium; Drug Combinations; Drug Stability; Drug Storage; Excipients; Felodipine; Humans; Hypoglycemic Agents; Hypromellose Derivatives; Male; Methylcellulose; Permeability; Pioglitazone; Polyvinyls; Species Specificity; Swine; Tablets; Thiazolidinediones; Time Factors; Young Adult

Rauvolfia serpentina (L). Benth. ex Kurz. (Apocynaceae) possessing antibacterial properties are widely used in modern herbal medicines. Curcuma longa L. (Zingiberaceae), a readily available antiseptic, possess antioxidant, antibacterial, blood purifying and antiinflammatory properties and used in various skin creams. Azadirachta indica A. Juss. (Meliaceae) possess astringent, antiviral, discutient, stimulant and antibacterial properties and works excellently well against acne and keeps the skin healthy.. Acne is the common skin problem that 85% of the teenagers face today. In this study, poly herbal anti-acne face wash gels were prepared using two polymers Carbopol and hydroxy propyl methyl cellulose (HPMC) along with the extracts of plants Rawvolfia serpentina, Curcuma longa, and Azadiracta indica.. The gel formulations were prepared in four different concentrations of 50, 100, 200 mg/ml as Gel-CRB 100, Gel-HPMC 50, Gel-HPMC 100, Gel-HPMC 200, respectively. The formulations were tested for the anti-acne activity by turbidimetric method.. RESULTS showed that the gels were non-irritant, stable and posses anti-acne activity. The efficacy when tested with a standard was almost same to that of Clindamycin gel.. From this study, Gel-HPMC 100 was proved to be stable and considered as an effective herbal formulation for acne treatment.

Topics: Acne Vulgaris; Acrylic Resins; Adolescent; Animals; Anti-Infective Agents, Local; Azadirachta; Curcuma; Drug Compounding; Excipients; Face; Gels; Humans; Hypromellose Derivatives; Methylcellulose; Nephelometry and Turbidimetry; Phytotherapy; Plant Preparations; Polyvinyls; Rats; Rats, Wistar; Rauwolfia; Skin; Treatment Outcome

The aim of this study was to apply quality by design (QbD) for pharmaceutical development of felodipine solid mixture (FSM) containing hydrophilic carriers and/or polymeric surfactants, for easier development of controlled-release tablets of felodipine. The material attributes, the process parameters (CPP), and the critical quality attributes of the FSMs were identified. Box-Behnken experimental design was applied to develop space design and determine the control space of FSMs that have maximum solubility, maximum dissolution, and ability to inhibit felodipine crystallization from supersaturated solution. Material attributes and CPP studied were the amount of hydroxypropyl methylcellulose (HPMC; X(1)), amount of polymeric surfactants Inutec®SP1 (X(2)), amount of Pluronic®F-127 (X(3)) and preparation techniques, physical mixture (PM) or solvent evaporation (SE; X(4)). There is no proposed design space formed if the Pluronic® content was below 45.1 mg and if PM is used as the preparation technique. The operating ranges, for robust development of FSM of desired quality, of Pluronic®, Inutec®SP1, HPMC, and preparation technique, are 49-50, 16-23, 83-100 mg, and SE, respectively. The calculated value of f2 was 56.85, indicating that the release profile of the controlled-release (CR) tablet (CR-6) containing the optimized in situ-formed FSM was similar to that of the target release profile. Not only did the ternary mixture of Pluronic®, HPMC with Inutec®SP1 enhance the dissolution rate and inhibit crystallization of felodipine, but also they aided Carbopol®974 in controlling felodipine release from the tablet matrix. It could be concluded that a promising once-daily CR tablets of felodipine was successfully designed using QbD approach.

Topics: Acrylic Resins; Chemistry, Pharmaceutical; Crystallization; Delayed-Action Preparations; Excipients; Felodipine; Hypromellose Derivatives; Kinetics; Methylcellulose; Poloxamer; Polyvinyls; Solubility; Solvents; Tablets; Total Quality Management

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 authors aimed to produce a new tear substitute capable of providing both lubrication and nutrition, based on a novel nutrient-containing therapeutic ocular surface medium (TOSM).. Viscous substances, including hypromellose (HPMC), carbopol, and sodium hyaluronate (SH) were added to the TOSM at various concentrations. Three commercial preservative-free artificial tear substitutes, Hypromellose (Pharmacy of Moorfields Eye Hospital, London, UK), Thilo-Tears (a carbomer; Alcon Pharma GmbH, Freiburg, Germany), and Vislube (a hyaluronate; Chemedica AG, Munich, Germany) were used as control preparations. Their viscosity and surface tension were measured. Human corneal (HCE-T) and conjunctival (IOBA-NHC) cell lines were used to investigate cell proliferation and viability in response to the formulations by means of a luminescence-based ATP assay and a calcein AM/EthD-1 assay.. HPMC, carbopol, and SH increased the viscosity of TOSM significantly. The surface tension of TOSM was reduced by HPMC, but not by carbopol or SH. TOSM-HPMC supported cell proliferation and viability better than TOSM-carbopol and TOSM-SH. TOSM-HPMC and TOSM-carbopol supported cell proliferation significantly better than the corresponding commercial artificial tears. However, TOSM-Vislube supported cell growth significantly better than TOSM-SH.. TOSM-HPMC showed superior lubricant and nutrient properties with moderate viscosity and little cytotoxicity. It thus could be an ideal nutrient and lubricant tear substitute for dry eyes and should be evaluated in a clinical study.

Topics: Acrylic Resins; Adenosine Triphosphate; Cell Line; Cell Proliferation; Cell Survival; Conjunctiva; Dose-Response Relationship, Drug; Epithelium; Epithelium, Corneal; Fluoresceins; Humans; Hyaluronic Acid; Hydrogen-Ion Concentration; Hypromellose Derivatives; Lubricants; Methylcellulose; Nutritional Physiological Phenomena; Ophthalmic Solutions; Osmolar Concentration; Polyvinyls; Surface Tension; Viscosity

Mucoadhesive polymer-coated pellets containing metformin hydrochloride were prepared by the powder-layering technique using a centrifugal fluidizing (CF)-granulator. Four high-viscosity polymers were applied to make the pellets: 1) hydroxymethylcellulose (HPMC), 2) sodium alginate (Na-Alg), 3) HPMC/Carbopol, and 4) sodium carboxylmethylcellulose (Na-CMC). The physical crushing test, mucoadhesive test, zeta-potential test, in vitro release study and observation of gastroretention state of the dosage form were performed to investigate the pellets. The strong adhesive interaction between the Na-CMC-coated pellets and the mucin disc was obtained by mucoadhesive test. Na-Alg was most effective among the polymers used in changing the value of zeta potential of the mucin solution by the interaction between a polymer and a mucin particle. Results from drug dissolution study showed that over 95% of the drug from all the four pellets was released before 2 h, while Na-CMC- and Na-Alg-coated pellets showed a moderate sustained-release in SGF (simulated gastric fluid) and SIF (simulated intestine fluid), respectively. In conclusion, Na-CMC and Na-Alg seem to be promising candidates for mucoadhesive formulation and further studies to improve the sustained-release property are underway for achieving the ultimate goal of once-a-day formulation of metformin hydrochloride.

Topics: Acrylic Resins; Adhesiveness; Alginates; Animals; Capsules; Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Gastric Mucosa; Glucuronic Acid; Hardness; Hexuronic Acids; Hypoglycemic Agents; Hypromellose Derivatives; Kinetics; Metformin; Methylcellulose; Mucins; Polymers; Polyvinyls; Powders; Rats; Solubility; Viscosity

Fluconazole mucoadhesive buccal films were prepared using film forming polymers namely; hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose (HEC), chitosan, Eudragit and sodium alginate (SALG) either alone or in combination with bioadhesive polymers. The bioadhesive polymers studied were sodium carboxymethyl cellulose (SCMC), Carbopol 974P, and polycarbophil (AA-A). The prepared films were characterized by means of film thickness, surface pH, swelling capacity, in vitro adhesion, in vivo residence time, in vitro drug release and in vivo drug release to determine the amount of drug release from selected film formulae using microbiological assay and HPLC. Optimum release behavior, convenient bioadhesion, acceptable elasticity were exhibited by film containing 2% HPMC and 1% SCMC (fresh or stored for 6 months). Determination of the amount of drug released in saliva after application of the selected fluconazole films confirmed the ability of the film to deliver the drug over a period of approximately 300 minutes and to reduce side effects and possibility of drug interaction encountered during systemic therapy of fluconazole, which would be beneficial in the case of oral candidiasis.

Topics: Acrylic Resins; Adhesiveness; Adult; Alginates; Antifungal Agents; Candidiasis, Oral; Carboxymethylcellulose Sodium; Cheek; Female; Fluconazole; Glucuronic Acid; Hexuronic Acids; Humans; Hypromellose Derivatives; Male; Methylcellulose; Polyvinyls; Solubility

This paper describes the development of an ex vivo perfusion method for the evaluation of topical ophthalmic formulations. The perfusion system developed consisted of a perfusion chamber, two precision pumps to control the in/out flow rates to simulate the tear flow rate, and a fluorescence microscope imager. Freshly excised rat cornea was used as a biomembrane. Fluorescein (FITC) was used as a marker. Residence time was determined by measuring fluorescence intensity over time after application of the formulation to the cornea. In addition, viscoelastic properties of the formulations were measured and correlated to the retention times. The perfusion method easily differentiated formulations based on the retention time on the cornea: For example, a 0.3% hydroxypropyl methylcellulose formulation had a short retention time of <10 min. Addition of 0.25% carboxymethylcellulose increased the retention time from less than 10 min to over 16 min, and addition of 0.1% Carbopol further increased retention time to over 40 min. For alginate formulations, the retention time was significantly longer in the presence of 0.06% calcium chloride than that of 0.006% calcium chloride. The longer residence time at a higher Ca++ concentration can be attributed to the greater elastic modulus associated with the gel. Interestingly, however, a hyaluronate formulation displayed a very long retention time but has low viscoelastic moduli. This suggests that the mucoadhesive properties may not always be discernable by the rheological properties. The ex vivo perfusion method may in fact provide more meaningful information with regard to retention times of formulations.

Topics: Acrylic Resins; Administration, Topical; Alginates; Animals; Chemistry, Pharmaceutical; Cornea; Elasticity; Excipients; Hypromellose Derivatives; In Vitro Techniques; Male; Methylcellulose; Models, Statistical; Mucins; Ophthalmic Solutions; Pharmaceutical Solutions; Polyvinyls; Rats; Rheology; Spectrometry, Fluorescence; Viscosity

The purpose of this study was to develop a pH-triggered in situ gelling vehicle for ophthalmic delivery of puerarin. The effect of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the aqueous solubility and in vitro corneal permeation of puerarin was also investigated. The puerarin solubility increased linearly and proportionally to the HP-beta-CD concentrations and 5% (w/v) HP-beta-CD enhanced its ocular permeability significantly. Carbopol 980NF was used as the gelling agent in combination with HPMC (Methocel E4M) which acted as a viscosity-enhancing agent. The optimum concentrations of Carbopol 980NF and HPMC E4M for the in situ gel-forming delivery systems were 0.1% (w/v) and 0.4% (w/v), respectively. When these two vehicles were combined, an in situ gel that had the appropriate gel strength and gelling capacity under physiological condition could be obtained. This combined solution could flow freely under non- physiological condition and showed the character of pseudoplastic fluid under both conditions. Both in vitro release studies and in vivo pharmacokinetics studies indicated that the combined polymer systems performed better in retaining puerarin than puerarin eye drops did. These results demonstrate that the Carbopol 980NF/HPMC E4M can be a viable alternative to conventional puerarin eye drops to enhance ocular bioavailability and patient compliance.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acrylic Resins; Animals; beta-Cyclodextrins; Biological Availability; Cell Membrane Permeability; Cornea; Drug Carriers; Drug Delivery Systems; Female; Gels; Hydrogen-Ion Concentration; Hypromellose Derivatives; In Vitro Techniques; Isoflavones; Male; Methylcellulose; Ophthalmic Solutions; Polymers; Polyvinyls; Rabbits; Solubility; Vasodilator Agents; Viscosity

Using the casting method novel mucoadhesive polymer blend film consisting of Carbopol, poloxamer, and hydroxypropylmethylcellulose (HPMC) was prepared and characterized. Triamcinolone acetonide (TAA) was loaded into Carbopol/poloxamer/HPMC polymer blend film. Carbonyl band of Carbopol in Carbopol/poloxamer/HPMC shifted to longer wavenumber than that of Carbopol in Carbopol/poloxamer due to the hydrogen bonding among Carbopol, poloxamer, and HPMC. Tan delta peak assigned to glass transition temperature (Tg) of HPMC shifted to low temperature due to increased flexibility caused by increased poloxamer content in polymer blend films. Swelling ratio of Carbopol/poloxamer/HPMC films was lowest in Carbopoll poloxamer/HPMC at mixing ratio of 35/30/35 (wt/wt/wt). Adhesive force of Carbopol/poloxamer/HPMC films increased with increasing HPMC content in Carbopol/poloxamer/HPMC polymer blend film and increasing hydroxypropyl group content in HPMC due to hydrophobic property of HPMC although bioadhesive force was highest at mixing ratio of 35/30/35 (wt/wt/ wt). Release of TAA from TAA-loaded Carbopol/poloxamer/HPMC polymer blend film in vitro increased with increasing loading content of drug.

Topics: Acrylic Resins; Adhesiveness; Drug Delivery Systems; Hypromellose Derivatives; Methylcellulose; Mucous Membrane; Poloxamer; Polyvinyls; Spectroscopy, Fourier Transform Infrared; Triamcinolone Acetonide

The major purpose of this study was to develop and characterize a series of carbopol- and methyl cellulose-based solutions as the in situ gelling vehicles for ophthalmic drug delivery. The rheological properties, in vitro release as well as in vivo pharmacological response of a combination of polymer solutions, including carbopol and methyl cellulose, were evaluated. It was found that the optimum concentration of carbopol solution for the in situ gel-forming delivery systems was 0.3% (w/w), and that for methyl cellulose solution was 1.5% (w/w). The mixture of 0.3% carbopol and 1.5% methyl cellulose solutions showed a significant enhancement in gel strength in the physiological condition; this gel mixture was also found to be free flowing at pH 4.0 and 25 degrees C. The rheological behaviors of carbopol/methyl cellulose solution were not affected by the incorporation of the drug. Drug levels in the aqueous humor of the rabbits were well above the MIC-values of relevant bacteria after 12 hours, the results of an optimized formulation containing 0.18% of pefloxacin mesylate compared well with the 0.3% marketed eye drop formulation, indicating our formulation to be significantly better considering that a similar effect was obtained at half the concentration. Both the in vitro release and in vivo pharmacological studies indicated that the carbopol/methyl cellulose solution had better ability to retain drug than did the carbopol or methyl cellulose solutions alone. The results demonstrated that the carbopol/methyl cellulose mixture can be used as an in situ gelling vehicle to enhance the ocular bioavailability of pefloxacin mesylate.

Topics: Acrylic Resins; Animals; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Drug Evaluation, Preclinical; Fluoroquinolones; Male; Methylcellulose; Models, Biological; Ophthalmic Solutions; Pefloxacin; Polyvinyls; Rabbits; Time Factors

The aim of this study was to add knowledge to the existing theories of mucoadhesion and to review mucoadhesive polymers based on their ability to form non-covalent bonds with mucus glycoprotein. Resonant mirror biosensor was used to study the candidate mucoadhesive polymers hydroxypropyl methylcellulose, carboxymethylcellulose, Carbopol, hyaluronate, alginate and chitosan. Bovine submaxillary mucin was chosen as substrate, representing the major glycosylated protein in mucus. For comparison, non-glycosylated bovine serum albumin was used as an alternative substrate. The results of this study reveal that there is a clear correlation between the ionization state of the polymer, which is dependent on the pH of the surrounding environment, and its binding behavior. Ionizable polymers need to be in their unionized state to be able to form non-covalent bonds with mucus glycoprotein. Acidic polymers display binding behavior only at pH around or lower than their corresponding pK(a) values and basic polymers vice versa. Chitosan was found to be the most mucoadhesive polymer. Unionizable polymers like hydroxypropyl methylcellulose did not display any affinity for mucus glycoprotein. Unionized amino- and carboxyl groups on polymers were found to be important structural feature of polymer for the formation of weak chemical bonds to mucus glycoproteins.

Topics: Acrylic Resins; Adhesiveness; Alginates; Animals; Binding, Competitive; Biosensing Techniques; Carboxymethylcellulose Sodium; Cattle; Chitosan; Glucosamine; Glycoproteins; Hyaluronic Acid; Hydrogen-Ion Concentration; Lactose; Methylcellulose; Molecular Structure; Mucins; Mucus; Polyvinyls; Protein Binding; Serum Albumin, Bovine; Technology, Pharmaceutical

In the present study, we prepared solid dispersions of the poorly water-soluble drug nitrendipine (NIT) using the twin screw extruder method with high-molecular-weight substances, hydroxypropylmethylcellulosephthalate (HPMCP) and Carbopol (CAR), as carriers. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) evaluation showed that solid dispersions can be formed when NIT-HPMCP and NIT-CAR mixtures are treated with the twin screw extruder method. Fourier Transformation IR Spectroscopy (FT-IR) obtained with NIT-HPMCP and NIT-CAR solid dispersions indicated the presence of hydrogen bonding between the drug and the carriers. NIT-CAR solid dispersions were found to give somewhat higher dissolution than crystalline NIT and physical mixtures, while the dissolution of NIT-HPMCP solid dispersions was markedly decreased compared with the crystalline NIT and physical mixtures. These findings indicated that CAR has a greater ability to improve the dissolution of NIT than HPMCP when a twin screw extruder was employed to prepare the solid dispersions. The twin screw extruder method can be used as a simple and effective method for the preparation of solid dispersions to improve the dissolution properties of poorly water-soluble drugs when choosing proper polymers as carriers.

Topics: Acrylic Resins; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Crystallization; Drug Carriers; Hydrogen Bonding; Methylcellulose; Molecular Structure; Molecular Weight; Nitrendipine; Polyvinyls; Solubility; Spectroscopy, Fourier Transform Infrared; Technology, Pharmaceutical; X-Ray Diffraction

The release profile of sodium dodecyl sulfate (SDS), a potent microbicide, from a female controlled drug delivery system (FcDDS) made of Carbopol 934P and hydroxypropyl methylcellulose (HPMC) was evaluated using a newly developed in vitro Simulant Vaginal System (SVS). The major parameters involved in the release profiles of SDS were categorized as: (1) formulation variables (total loading weight of intravaginal delivery systems, SDS loading doses in intravaginal delivery systems); (2) intrinsic variables (vaginal fluid secretion rate, vaginal fluid pH); and (3) extrinsic variables (inserting position). In most conditions, about 70% of the loading dose of SDS was released from FcDDS within 6h of application. The release profile showed that concentrations needed for complete human papilloma virus (HPV) inactivation could be obtained within 10 min after the application. It was demonstrated that intrinsic variables (i.e., the rate and pH of vaginal fluid) played an integral role in determining the release profile of SDS, while loading dose of SDS in FcDDS did not significantly affect the percentage of the total amount of SDS released. It can be concluded that FcDDS can be exploited as a controlled delivery device for prevention against sexually transmitted diseases.

Topics: Acrylic Resins; Administration, Intravaginal; Algorithms; Anti-Infective Agents; Buffers; Diffusion; Drug Delivery Systems; Excipients; Female; Humans; Hydrogen-Ion Concentration; Lactose; Methylcellulose; Oxazines; Papillomaviridae; Polyvinyls; Sodium Dodecyl Sulfate

The purpose of this study is to investigate the effect of formulation variables on drug release and floating properties of the delivery system. Hydroxypropyl methylcellulose (HPMC) of different viscosity grades and Carbopol 934P (CP934) were used in formulating the Gastric Floating Drug Delivery System (GFDDS) employing 2 x 3 full factorial design. Main effects and interaction terms of the formulation variables could be evaluated quantitatively by a mathematical model. It was found that both HPMC viscosity, the presence of Carbopol and their interaction had significant impact on the release and floating properties of the delivery system. The decrease in the release rate was observed with an increase in the viscosity of the polymeric system. Polymer with lower viscosity (HPMC K100LV) was shown to be beneficial than higher viscosity polymer (K4M) in improving the floating properties of GFDDS. Incorporation of Carbopol, however, was found to compromise the floating capacity of GFDDS and release rate of calcium. The observed difference in the drug release and the floating properties of GFDDS could be attributed to the difference in the basic properties of three polymers (HPMC K4M, K100LV and CP934) due to their water uptake potential and functional group substitution.

Topics: Absorption; Acrylic Resins; Biological Availability; Calcium Carbonate; Capsules; Delayed-Action Preparations; Drug Delivery Systems; Humidity; Hypromellose Derivatives; Kinetics; Methylcellulose; Multivariate Analysis; Pharmaceutic Aids; Polyvinyls; Solubility; Viscosity; Water

A modified release bi-layered tablet of melatonin incorporating a fast release fraction consisting of melatonin-beta-cyclodextrin inclusion complex and a slow release fraction containing melatonin in HPMC K15M and Carbopol 971 P matrices was prepared. The formulation developed showed an initial burst followed by a near zero order release pattern for a period of 8 h. The drug content, physical characteristics and the release profile were unaffected after 3 months of an accelerated stability study at 40 degrees C and 75% relative humidity.

Topics: Acrylic Resins; Antioxidants; beta-Cyclodextrins; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Cyclodextrins; Delayed-Action Preparations; Drug Stability; Excipients; Kinetics; Lactose; Melatonin; Methylcellulose; Microscopy, Electron, Scanning; Oxazines; Polyvinyls; Solubility; Spectroscopy, Fourier Transform Infrared; Tablets

A polymeric film composed of Carbopol, Poloxamer and hydroxypropyl methylcellulose was prepared to develop a buccal patch and the effects of composition of the film on adhesion time, swelling ratio, and dissolution of the film were studied. The effects of plasticizers or penetration enhancers on the release of triamcinolone acetonide (TAA) were also studied. The hydrogen bonding between Carbopol and Poloxamer played important role in reducing swelling ratio and dissolution rate of polymer film and increasing adhesion time. The swelling ratio of the composite film was significantly reduced and the adhesion time was increased when compared with Carbopol film. As the ratio of Poloxamer to hydroxypropyl methylcellulose increased from 0/66 to 33/33, the release rate of TAA decreased. However, no further significant decrease of release rate was observed beyond the ratio of 33/33. The release rate of TAA in the polymeric film containing polyethylene glycol 400, a plasticizer, showed the highest release rate followed by triethyl citrate, and castor oil. The release rate of TAA from the polymeric film containing permeation enhancers was slower than that from the control without enhancers. Therefore, these observations indicated that a preparation of a buccal patch is feasible with the polymeric film composed of Cabopol, Poloxamer and hydropropyl methylcellulose.

Topics: Acrylic Resins; Adhesives; Administration, Buccal; Hypromellose Derivatives; Methylcellulose; Mouth Mucosa; Poloxamer; Polyvinyls; Solubility

To evaluate the contribution of formulation variables on the floating properties of a gastric floating drug delivery system (GFDDS) using a continuous floating monitoring system and statistical experimental design.. A modified continuous floating monitoring system, which consisted of an electric balance interfacing with a PC, was designed to perform the continuous monitoring of floating kinetics of GFDDS. Several formulation variables, such as different types of hydroxypropyl methylcellulose (HPMC), varying HPMC/Carbopol ratio, and addition of magnesium stearate, were evaluated using Taguchi design, and the effects of these variables were subjected to statistical analysis.. The continuous floating monitoring system developed was validated, using capsules with different density, and a good correlation between theoretical and experimental values was obtained (R2 = 0.9998), indicating the validity of the setup. The statistical analysis indicated that magnesium stearate had a significant effect on the floating property of GFDDS (p < 0.05), and addition of magnesium stearate could significantly improve the floating capacity of the GFDDS. It was found that the HPMC of higher viscosity grade generally exhibited a greater floating capacity, but the effect was not statistically significant. For polymers with the same viscosity, i.e., K4M and E4M, the degree of substitution of the function group did not show any significant contribution. A better floating behavior was achieved at higher HPMC/Carbopol ratio. Carbopol appeared to have a negative effect on the floating behavior of GFDDS.. It was concluded that by using a validated continuous floating monitoring system, the effect of formulation variables on the floating property of the delivery system and their ranges could be identified. Incorporation of hydrophobic agents, such as magnesium stearate, could significantly improve the floating capacity of the GFDDS.

Topics: Acrylic Resins; Analysis of Variance; Chemistry, Pharmaceutical; Drug Delivery Systems; Kinetics; Lactose; Methylcellulose; Oxazines; Polyvinyls

To prepare buspirone hydrochloride buccal adhesive tablet and investigate factors that influence drug release behavior and the drug release mechanism.. Buspirone hydrochloride buccal adhesive tablet was prepared with double layers structure composed of drug core and adhesive layer. The materials of the drug core were carbopol 974 and lactose, the adhesive layers were carbopol 974 and HPMC K4M. The influence of drug release factors such as adhesive layer component, adhesive layer weight and adhesive tablet hardness was investigated. The relationship between adhesive layer weight and drug release mechanism in vitro was studied.. The results showed that the weight of the adhesive layer and the hardness of adhesive tablet showed significant effects on drug release, but the adhesive layer component showed no significant effect. The optimum prescription of buspirone hydrochloride buccal adhesive tablet was carbopol: HPMC = 1:1, adhesive layer weight = 50%, and adhesive tablet hardness = 4 kg. The study of drug release mechanism from adhesive tablet showed that it was double directions when adhesive layer weight was 20%, and single direction first then double directions when 33.33%, and single direction all along when 50%.. The speed and direction of drug release from adhesive tablet can be controlled by regulating adhesive layer weight.

Topics: Acrylic Resins; Adhesiveness; Administration, Buccal; Anti-Anxiety Agents; Buspirone; Delayed-Action Preparations; Drug Carriers; Hardness; Lactose; Methylcellulose; Oxazines; Polyvinyls; Tablets; Technology, Pharmaceutical

The impact of controlled release (CR) formulations having different gel strength values (gamma) on in vivo tablet performance and the in vitro/in vivo correlation of the formulations was investigated. The CR tablets containing either hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), or carbomer were formulated with theophylline and Fast Flo lactose to produce tablets with a polymer content of 8 and 30% w/w. gamma was measured using a previously reported method. Male beagle dogs were utilized. Results showed that dissolution profiles were similar for all three polymers at the same % w/w level of polymer, irrespective of media (DI H2O, 0.1 N HCl, and pH 6.8 phosphate buffer). Mean gamma values were significantly different (p < or = 0.05) and were in order of HPMC K100MP > HPC HXF > carbomer 971P (same 30% w/w) with absolute gamma values at 30% w/w in DI H2O of 6600, 4600, and 1600 ergs/cm3, respectively. Drug profiles in plasma for the 30% HPMC K100MP tablets were consistent with in vitro dissolution profiles and gamma values. Plasma profiles for the 30% HPC HXF tablets were similar in vivo as the HPMC tablets. Plasma profiles for the 30% carbomer 971P formulation showed much higher drug concentrations (compared to HPMC and HPC) in vivo in all dogs. This findings is not consistent with the slow drug release found in the dissolution profiles but consistent with its low in vitro gamma values. Assessment of the predictability of a level A in vitro/in vivo correlation was quantified by absolute mean percent prediction error (PE). Formulations having gamma approximately 6000 ergs/cm3 have acceptable PE < 20%, and low standard deviation (sigma). Results showed that gamma values of CR hydrogel tablets in vitro will affect the in vivo performance (i.e., absorption kinetics of the drug) of the tablets and were also found to better assess (compared to in vitro dissolution profiles alone) the predictability of in vitro/in vivo correlations (level A and multiple level C).

Topics: Acrylic Resins; Animals; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dogs; Hydrogel, Polyethylene Glycol Dimethacrylate; Lactose; Male; Methylcellulose; Oxazines; Polyvinyls; Solubility; Tablets; Theophylline

To investigate bioadhesion of carbopol and hydroxypropyl methylcellulose of different viscosity grade to rat gastrointestinal mucosa.. The maximum adhesion force has been adopted as an index of adhesive evaluation in vitro, gastro-emptying rate and migrating length in intestine have been adopted as an index of adhesive evaluation in vivo.. In vitro adhesion studies indicated that the adhesive force of low-vicosity materials was stronger than that of high-vicosity materials, while the transferation rate of high-vicosity materials is significantly higher compared to that of low-vicosity materials in vivo.. Adhesive force of materials gives no correlation with rate of the materials in rat; Cb934 have the optium bioadhesion among the studied materials and can be used as the preferred adjuvant in oral bioadhesion preparation.

Topics: Acrylic Resins; Adhesiveness; Animals; Drug Carriers; Gastric Emptying; Gastric Mucosa; Gastrointestinal Transit; Hypromellose Derivatives; Intestinal Mucosa; Methylcellulose; Polyvinyls; Rats; Rats, Wistar; Viscosity

Controlled release buccal patches were fabricated using Eudragit NE40D and studied. Various bioadhesive polymers, namely hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose and Carbopol of different grades, were incorporated into the patches, to modify their bioadhesive properties as well as the rate of drug release, using metoprolol tartrate as the model drug. The in-vitro drug release was determined using the USP 23 dissolution test apparatus 5 with slight modification, while the bioadhesive properties were evaluated using texture analyzer equipment with chicken pouch as the model tissue. The incorporation of hydrophilic polymers was found to affect the drug release as well as enhance the bioadhesiveness. Although high viscosity polymers can enhance the bioadhesiveness of the patches, they also tend to cause non-homogeneous distribution of the polymers and drug, resulting in non-predictable drug-release rates. Of the various bioadhesive polymers studied, Cekol 700 appeared to be most satisfactory in terms of modifying the drug release and enhancement of the bioadhesive properties.

Topics: Acrylic Resins; Adhesiveness; Administration, Topical; Animals; Carboxymethylcellulose Sodium; Chickens; Delayed-Action Preparations; Drug Delivery Systems; Drug Design; In Vitro Techniques; Lactose; Methylcellulose; Models, Biological; Mouth Mucosa; Oxazines; Polymers; Polyvinyls; Solubility; Viscosity

In this study, roller-compaction of acetaminophene was studied to model the effect of binder type (hydroxypropyl methyl cellulose (HPMC), polyethylene glycol (PEG), Carbopol), binder concentration (5, 10 and 20%), number of roller-compaction passes (one or two), and extragranular microcrystalline cellulose addition on the properties of compressed tablets. Forty-two batches resulted from the experimental design. The artificial neural network methodology (ANN) along with genetic algorithms were used for data analysis and optimization. ANN and genetic models provided R2 values between 0.3593 and 0.9991 for measured responses. When a set of validation experiments was analyzed, genetic algorithm predictions of tablet characteristics were much better than the ANN. Optimization based on genetic algorithm showed that using HPMC at 20%, with two roller-compaction passes would produce mechanically acceptable acetaminophene tablets. PEG and carbopol would also produce acceptable tablets perhaps more suitable for sustained release applications. Using PEG as a binder had the additional advantage of not requiring an external lubricant during tablet manufacturing.

Topics: Acetaminophen; Acrylic Resins; Algorithms; Analgesics, Non-Narcotic; Cellulose; Chemistry, Pharmaceutical; Compressive Strength; Elasticity; Excipients; Hypromellose Derivatives; Methylcellulose; Models, Chemical; Models, Genetic; Neural Networks, Computer; Polyethylene Glycols; Polyvinyls; Predictive Value of Tests; Tablets

To evaluate the additional effect of bioadhesives in combination with iotrolan and barium as oral contrast media in an animal model.. The bioadhesives Noveon, CMC, Tylose and Carbopol 934 were added to iotrolan and barium. The solutions were administered to rabbits by a feeding tube. The animals were investigated by computed tomography (CT) and radiography after 0.5, 4, 12, 24 and in part after 48 hours. Mucosal coating and contrast filling of the bowel were evaluated.. Addition of bioadhesives to oral contrast media effected long-term contrast in the small intestine and colon, but no improvement in continuous filling and coating of the gastrointestinal tract was detected. Mucosal coating was seen only in short regions of the caecum and small intestine. In CT the best results for coating were observed with tylose and CMC, in radiography additionally with carbopol and noveon. All contrast medium were well tolerated.. The evaluated contrast medium solutions with bioadhesives have shown long-term contrast but no improvement in coating in comparison to conventional oral contrast media.

Topics: Acrylic Resins; Adhesiveness; Adhesives; Administration, Oral; Animals; Barium Sulfate; Carboxymethylcellulose Sodium; Contrast Media; Digestive System; Drug Carriers; Drug Evaluation; Gels; Methylcellulose; Pharmaceutic Aids; Polyvinyls; Rabbits; Tomography, X-Ray Computed; Triiodobenzoic Acids

Aqueous solutions of Carbopol [polyacrylic acid (PAA)] are low viscosity acidic solutions that transform into gels upon an increase in the pH and, therefore, may be used as in situ gelling ophthalmic drug delivery systems. However, the amount of PAA required in the solution to form stiff gels upon installation in the eye is not easily neutralized by the buffering action of tear fluid. A reduction in the PAA concentration without comprising the in situ gelling properties as well as the overall rheological behavior of the system can be achieved by adding a suitable viscosity-enhancing polymer. The rheological properties of aqueous solutions containing PAA and hydroxypropyl methylcellulose (HPMC), a viscosity-enhancing polymer, evaluated as a function of temperature and pH, were similar to those of pure PAA solutions; that is, both form low viscosity liquids at pH 4.0 and transform into stiff gels with plastic rheological behavior and comparable viscosities upon increasing the pH to 7.4. In addition, HPMC-PAA gels show slow in vitro release of incorporated timolol maleate. Thus, the HPMC-PAA combination demonstrates properties suitable for formulation as a liquid ophthalmic delivery systems, which upon instillation into the cul-de-sac of the eye can undergo in situ phase transition to form gels capable of sustained drug release.

Topics: Acrylic Resins; Chromatography, High Pressure Liquid; Gels; Hydrogen-Ion Concentration; Hypromellose Derivatives; Methylcellulose; Ophthalmic Solutions; Polyvinyls; Temperature; Time Factors

The in-vitro effectiveness of polyacrylic acid polymers in inhibiting degradation of insulin, calcitonin, and insulin-like growth factor-I by colonic lumenal contents was determined. Further, the effect of Carbopol 974P, a polyacrylic acid polymer, on colonic absorption of insulin in rats was studied. The results revealed that Carbopol 934P, 971P, and 974P all strongly inhibited microbial proteolytic activities against insulin, calcitonin, and insulin-like growth factor-I. Inhibition by Carbopol polymers was complete or almost complete when the concentration of each polymer in saline or in 50 or 100 mM Tris buffer was 0.4%, where the pH of the medium was lower than 5. The extensive inhibition by these polyacrylic acid polymers seems to correlate with their ability to acidify the incubation medium. Further, in-situ absorption studies showed that Carbopol 974P increased the pharmacological availability of colonic insulin. In summary, Carbopol polymers are useful in minimizing colonic proteolysis of peptide drugs.

Topics: Acrylic Resins; Animals; Calcitonin; Colon; Hydrogen-Ion Concentration; Hypoglycemic Agents; Hypromellose Derivatives; Insulin; Insulin-Like Growth Factor I; Intestinal Absorption; Male; Methylcellulose; Peptides; Pharmaceutic Aids; Polyvinyls; Protease Inhibitors; Rats; Rats, Sprague-Dawley

Buccoadhesive controlled-release systems for the delivery of morphine sulfate were prepared by compression of hydroxypropyl methylcellulose (HPMC) with carbomer (CP), which served as the bioactive adhesive compound. The release behavior of systems containing 30 mg of morphine sulfate and various amounts of the two polymers was found to be non-Fickian. The adhesion force was significantly affected by the mixing ratio of HPMC and CP in the tablet, and the weakest adhesion force was observed at a ratio of 1:1 (HPMC:CP). Interpolymer complex formation was confirmed between HPMC and CP in acidic medium by turbidity, viscosity, and FT-IR measurements. The amount absorbed (percentage of the drug loaded) of the controlled-release buccoadhesive tablets in six healthy volunteers and was 30 +/- 5%.

Topics: Absorption; Acrylic Resins; Administration, Buccal; Adult; Analysis of Variance; Animals; Cattle; Delayed-Action Preparations; Female; Humans; Hypromellose Derivatives; In Vitro Techniques; Male; Methylcellulose; Morphine; Mouth Mucosa; Nephelometry and Turbidimetry; Polymers; Polyvinyls; Spectroscopy, Fourier Transform Infrared; Tablets; Viscosity

Poor bioavailability of ophthalmic solutions caused by dilution and drainage from the eye can be overcome by using in situ-forming ophthalmic drug delivery systems prepared from polymers that exhibit reversible phase transitions. Joshi et al. (1), have demonstrated that aqueous compositions that reversibly gel in response to simultaneous variations in at least two physical parameters, such as temperature, pH, and ionic strength, can be formed by appropriate combinations of macromolecular polymers which exhibit reversible gelation properties. In the present study, the rheological characterization of such a system, prepared by a combination of Carbopol (C) and methyl cellulose (MC), was carried out at two different pH (4.0 and 7.4) and temperatures (25 and 37 degrees C) by rotational cone and plate viscometry. The shear stress (tau) vs. shear rate (D) flow curves of the aqueous polymer solutions indicated a pseudoplastic behavior, with a yield point. An increase in pH from 4.0 to 7.4, or temperature from 25 to 37 degrees C, resulted in an increase in viscosity (eta), tau, and yield point, the magnitude of changes being highest when both the parameters were altered simultaneously. An increase in concentration of either C or MC, or an increase in MC molecular weight results in an increase in eta, tau, and yield point. Among the compositions studied, a solution containing 1.5% MC 0.3% C was found to have low eta, and formed a strong gel under simulated physiological conditions. Such a system can be formulated as drug containing liquid suitable for administration by instillation into the eye, which upon exposure to physiological conditions will shift to the gel (semi-solid) phase, thus increasing the precorneal residence time of the delivery system and enhancing ocular bioavailability.

Topics: Acrylic Resins; Biological Availability; Drug Delivery Systems; Gels; In Vitro Techniques; Methylcellulose; Ophthalmic Solutions; Polyvinyls; Rheology; Temperature; Viscosity

A polymer carrier system was developed to reduce the bitterness of erythromycin and its 6-O-methyl derivative, clarithromycin, by absorption to Carbopol. The mechanism involves ionic bonding of the amine macrolide to the high molecular weight polyacrylic acid, thereby removing the drug from the solution phase in an ion-free suspension. After ingestion, endogenous cations displace the drug from the polymer in the gastrointestinal tract to achieve bioavailability. The macrolide-Carbopol complexes were prepared by dissolving or slurrying predetermined ratios of drug and polymer in water or hydroalcoholic mixtures. A series of in vitro equilibrium studies, taste screening, and bioavailability studies in dogs established the characteristics for the various drug-polymer ratios. Taste protection was further improved by encapsulating the adsorbate particles with polymer coatings. Hydroxypropyl methylcellulose phthalate (HP-55) provided the best combination of suspension stability, taste protection and bioavailability. Human bioavailability studies demonstrated that the microencapsulated Carbopol absorbates of erythromycin and clarithromycin gave blood levels comparable to those obtained from conventional solid formulations.

Topics: Absorption; Acrylic Resins; Animals; Anti-Bacterial Agents; Biological Availability; Clarithromycin; Dogs; Drug Carriers; Erythromycin; Humans; Methylcellulose; Polyvinyls; Taste