ethyl-cellulose and stearic-acid

As compared to the conventional standard chemotherapy of solid cancer such as lung, biochemical modulation (BCM) therapy has been proven to have a good therapeutic efficiency. BCM therapy uses the low dose and low infusion rate of anti-cancer drug. To increase of the QOL of cancer patients, oral BCM therapy is needed. For this purpose, two kinds of new oral sustained-release cisplatin preparations were developed, micro-porous CDDP capsule made of ethylcellulose(EC) and CDDP-EC-stearic acid solid dispersion. After oral administrations of these preparations, serum CDDP levels were maintained over 0.2 microgram/ml for 24h. Experimental therapy using P815 tumor cells transplanted mice suggested the usefulness of CDDP solid dispersion preparation.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Capsules; Cellulose; Cisplatin; Delayed-Action Preparations; Drug Delivery Systems; Drug Design; Humans; Mice; Neoplasms, Experimental; Stearic Acids

In the present study we have characterized the influence of the polymer gelator ethylcellulose (EC) on the crystallization behavior of mixtures of stearyl alcohol and stearic acid (SOSA). The presence of EC led to a more abrupt thermo-reversible crystallization process and an increase in the onset of crystallization temperature from 22.7±0.35°C to 26.5±0.42°C. X-ray analysis indicated that the polymorphism of the mixed SOSA crystals was maintained in the presence of EC; however, changes in the small angle region indicated the presence of the polymer network altered the higher-order organization of the crystal network. Significant changes in the microstructural organization were also observed by light microscopy. A random distribution of needle-like, oriented platelets were observed in SOSA gels, while branched, feather-like structures were apparent in the mixed EC/SOSA system. Temperature-sweep rheological experiments of the combined EC/SOSA system also indicated that prior to crystallizing, SOSA molecules plasticized the polymer chains, resulting in a decrease in the gelation point (cross-over point; G'=G″) from ~110°C to 90°C. This effect was corroborated by DSC experiments, in which it was observed that the glass transition temperature of EC decreased and broadened with increasing SOSA content. Back extrusion flow curves indicated that the addition of EC reduces the brittleness and increases the plasticity of the bulk material, as indicated by the brittleness factor quantified over the steady-state flow regime, even when the combined gelator system was substantially firmer. Although the presence of the EC network resulted in a stress overshoot during initial penetration, by incorporating EC below its critical gelation concentration eliminated the overshoot while still providing plasticity to the SOSA network, such that the flow behavior was shown to be comparable to several commercial margarines. This study has demonstrated the ability of EC to modify the crystallization behavior of a low molecular weight oleogelator, while increasing the plasticity of the polymer network, to form a synergistic oleogelator system.

Topics: Cellulose; Crystallization; Fatty Alcohols; Gels; Molecular Conformation; Plasticizers; Stearic Acids; Temperature

The research envisaged focuses on vital impacts of variegated lubricants, glidants and hydrophilic additives on lag time of press coated ethylcellulose (EC) tablets using prednisone as a model drug. Several lubricants and glidants such as magnesium stearate, colloidal SiO2, sodium stearyl fumarate, talc, stearic acid, polyethylene glycol (6000) and glyceryl behenate were investigated to understand their effects on lag time by changing their concentrations in outer coat. Further, the effects of hydrophilic additives on lag time were examined for hydroxypropylmethylcellulose (E5), hydroxypropylcellulose (EF and SSL), povidone (K30), copovidone, polyethylene glycol (4000), lactose and mannitol. In vitro drug release testing revealed that each selected lubricant/glidant, if present even at concentration of 0.25% w/w, significantly reduced the lag time of press coated tablets. Specifically, colloidal SiO2 and/or magnesium stearate were detrimental while other lubricants/glidants were relatively less injurious. Among hydrophilic additives, freely water soluble fillers had utmost influence in lag time, whereas, comparatively less impact was observed with polymeric binders. Concisely, glidant and lubricant should be chosen to have minimal impact on lag time and further judicious selection of hydrophilic additives should be exercised for modulating lag time of pulsatile release formulations.

Topics: Cellulose; Chemistry, Pharmaceutical; Excipients; Hydrophobic and Hydrophilic Interactions; Hypromellose Derivatives; Lactose; Lubricants; Mannitol; Polyethylene Glycols; Povidone; Prednisone; Silicon Dioxide; Solubility; Stearic Acids; Tablets

In this study a gastric-retentive delivery system was prepared by a novel method which is reported here for the first time. An innovative floating and bioadhesive drug delivery system with a hollow structure was designed and prepared. The floating and bioadhesive drug delivery system was composed of a hollow spherical shell, a waterproof layer (Stearic acid), a drug layer (Ofloxacin), a release retarding film (the novel blended coating materials) and a bioadhesive layer (Carbomer 934P) prepared by using a liquid multi-layering process. A novel blended coating material was designed and investigated to solve the problem of the initial burst release of the formulation and the release mechanism of the novel material was analyzed in this study. The optimized formulation provided the sustained release characteristic and was able to float for 24h. The SEM cross-section images showed that the particulates were hollow with a spherical shell. X-ray images and pharmacokinetic studies (Frel = 124.1 ± 28.9%) in vivo showed that the gastric-retentive delivery system can be retained in the stomach for more than 6h. The floating and bioadhesive particulate drug delivery system based on a hollow structure with a dual function presented here is a viable alternative to other for gastroretentive drug delivery system.

Topics: Acrylic Resins; Adhesiveness; Animals; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Delivery Systems; Drug Liberation; Gastric Mucosa; In Vitro Techniques; Male; Ofloxacin; Polymethacrylic Acids; Rabbits; Rats, Sprague-Dawley; Stearic Acids; Stomach

The objective of the present study was to develop pH-independent/dependent sustained release (SR) tablets of ondansetron HCl dihydrate (OND), a selective 5-HT3 receptor antagonist that is used for prevention of nausea and vomiting caused by chemotherapy, radiotherapy and postoperative treatment. The challenge with the OND API is its pH-dependent solubility and relatively short elimination half-life. Therefore, investigations were made to solve these problems in the current study. Formulations were prepared using stearic acid as a binding agent via a melt granulation process in a twin-screw extruder. The micro-environmental pH of the tablet was manipulated by the addition of fumaric acid to enhance the solubility and release of OND from the tablet. The in vitro release study demonstrated sustained release for 24h with 90% of drug release in formulations using stearic acid in combination with ethyl cellulose, whereas 100% drug release in 8h for stearic acid-hydroxypropylcellulose matrices. The formulation release kinetics was correlated to the Higuchi diffusion model and a non-Fickian drug release mechanism. The results of the present study demonstrated for the first time the pH dependent release from hydrophilic-lipid matrices as well as pH independent release from hydrophobic-lipid matrices for OND SR tablets manufactured by means of a continuous melt granulation technique utilizing a twin-screw extruder.

Topics: Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Compounding; Drug Liberation; Excipients; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Kinetics; Ondansetron; Serotonin Antagonists; Solubility; Stearic Acids; Tablets; Technology, Pharmaceutical

The aim of this study was to develop and optimize a segregation-free ethyl cellulose-coated extended release multiparticulate formulation to be compressed into tablets without affecting the drug release. Standard tableting excipients (e.g., microcrystalline cellulose, lactose or sorbitol) were layered onto ethyl cellulose-coated propranolol hydrochloride pellets to form a cushion layer in order to eliminate segregation problems normally resulting from particle size difference between coated pellets and excipient powders and second to protect the integrity of the brittle ethyl cellulose coating during compression. The disintegration behavior of the tablets depended strongly on the composition of the cushion layer. Rapid tablet disintegration was obtained with microcrystalline cellulose and the disintegrant sodium croscarmellose. However, the drug release from these cushion-layered pellets still increased upon compression. Incorporation of a glidant into the cushion layer or between the cushion layer and the ethyl cellulose coating reduced the compression effect on drug release markedly. Glidant-containing formulations showed a delayed deformation and damage of the ethyl cellulose-coated pellet upon mechanical stress. In summary, cushion layer based on microcrystalline cellulose facilitated segregation-free compression of a highly compression-sensitive extended release ethyl cellulose-coated pellets into fast-disintegrating and hard tablets without compromising the release properties of the multiparticulates. Directly compressible cushion-layered pellets protected the pellet coating significantly better from damages during tabletting when compared to the conventional compression of blends of coated pellets and excipient powders.

Topics: Carboxymethylcellulose Sodium; Cellulose; Delayed-Action Preparations; Drug Compounding; Excipients; Hardness; Lactose; Sorbitol; Stearic Acids; Tablets

The study was carried out to establish the effectiveness of a mixed film composed of ethylcellulose/Eudragit S100 for colonic delivery of 5-flourouracil (5-FU). Tablets cores containing 5-FU were prepared by direct compression method by coating at different levels (2-9%, m/m) with a non-aqueous solution containing ethylcellulose/Eudragit S100. Coated tablets were studied for the in vitro release of 5-FU and the samples were analyzed spectrophotometrically at 266 nm. Drug release from coated systems depended on the thickness of the mixed film and the composition of the core. Channel formation was initiated in the coat by dissolution of the Eudragit S100 fraction at higher pH in the colonic region. The release was found to be higher in tablets containing Avicel as filler owing to its wicking action compared to that from lactose containing cores. Furthermore, batches containing superdisintegrant (1%, m/m Cross-PVP) along with Avicel in the core released approximately 81.1% drug during the colonic transit time. Kinetic studies indicated that all the formulations followed first-order release kinetics. The developed delivery system will expectedly deliver the drug to the colon.

Topics: Antimetabolites, Antineoplastic; Cellulose; Colon; Colorectal Neoplasms; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Excipients; Fluorouracil; Hardness; Humans; Hydrogen-Ion Concentration; Lactose; Pharmacokinetics; Polymethacrylic Acids; Polyvinyls; Pressure; Pyrrolidines; Solubility; Stearic Acids; Tablets; Tablets, Enteric-Coated; Talc

Even though ion-exchange resins are good drug carriers to get sustained release properties, it may not be good enough only with themselves. For further sustained release effect, a diffusion barrier or coating on the resins' surface can be utilized. Initially, microencapsulation using a w/o/w double emulsion method was used to apply ethylcellulose (EC) onto the drug/resin complexes. Typical pharmaceutical waxes can be alternative materials to delay the drug release from the complex. After the coating, the coated resin particles were incorporated into fast-disintegrating tablets to get an idea regarding the effects of wet granulation and compression on the release. Among the different grades of ECs tested (Ethocel 20, 45, and 100), more viscous EC resulted in better morphologies and sustained release effects. Because the drug release rate was significantly dependent on the coating level, the release rate can be modified easily by changing different levels of the coating. The drug release rate was also strongly dependent on the granulation and compaction process as the coated particles were incorporated into the tablet dosage form. Among the tested waxes, stearic acid had an effect on the sustained release together with lubrication and wetting properties. Even though microencapsulation or wax coating may not be practical for real manufacturing, the results may give valuable information how to formulate sustained release dosage forms and their properties on the tablet preparation.

Topics: Algorithms; Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diffusion; Drug Carriers; Drug Compounding; Emulsions; Fatty Acids; Ion Exchange Resins; Microscopy, Electron, Scanning; Powders; Resins, Synthetic; Solubility; Solvents; Stearic Acids; Tablets; Waxes

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

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

A tablet system consisting of cores coated with two layers of swelling and rupturable coatings was prepared and evaluated as pulsatile drug delivery system. Cores containing buflomedil HCl as model drug were prepared by direct compression of different ratios of spray-dried lactose and microcrystalline cellulose and were then coated sequentially with an inner swelling layer containing a superdisintegrant (croscarmellose sodium) and an outer rupturable layer of ethylcellulose. The effect of core composition, level of swelling layer and rupturable coating, and magnesium stearate in rupturable layer was investigated. Mechanical properties of ethylcellulose films in the dry and wet state were characterized with a puncture test. Rupture and dissolution tests were performed using the USP XXIV paddle method at 50 rpm in 0.1 N HCl. The lag time of the pulsatile release tablets decreased with increasing amount of microcrystalline cellulose in the cores and increased with increasing levels of both swelling layer and rupturable ethylcellulose coating. Increasing levels of the ethylcellulose coating retarded the water uptake and thus prolonged the lag time. Addition of magnesium stearate to the ethylcellulose coating lowered the mechanical strength of the film and improved the robustness of the system.

Topics: Cellulose; Delayed-Action Preparations; Drug Delivery Systems; Hardness; Microscopy, Electron, Scanning; Pharmaceutic Aids; Povidone; Solubility; Stearic Acids; Surface Properties; Tablets; Water

The water-insoluble polymer ethylcellulose is used as a retardant to prepare the sustained release of potassium chloride microspheres by drying in a liquid process. The effect of sustained release of potassium from ethylcellulose microspheres was evaluated by the in vitro dissolution test, and was compared to a commercial product (Slow-K). The results showed that ethylcellulose microspheres loaded with potassium chloride could be easily prepared and satisfactory results could be obtained considering size distribution and shapes of microspheres by incorporating aluminum stearate. The encapsulation efficiency and loading capacity were about 84-93 and 36%, respectively. However, the potassium/ethylcellulose 2/2 (30-45 mesh) microspheres showed the similar sustained release effect of commercial product.

Topics: Acrylic Resins; Cellulose; Delayed-Action Preparations; Drug Carriers; Kinetics; Microscopy, Electron, Scanning; Microspheres; Particle Size; Potassium Chloride; Solubility; Stearic Acids; Surface Properties; Technology, Pharmaceutical

Chronopharmaceutical capsules, ethylcellulose-coated to prevent water ingress, exhibited clearly different release characteristics when coated by organic or aqueous processes. Organic-coated capsules produced a delayed pulse release, whereas aqueous-coated capsules exhibited less delayed and more erratic release behaviour. Nuclear magnetic resonance microscopy was used to elucidate the internal mechanisms underlying this behaviour by studying the routes of internal water transport and the timescale and sequence of events leading to the pulse. Images showed that the seal between the shell and the tablet plug is a key route of water penetration in these dosage forms. There is evidence for a more efficient seal in the organic-coated capsule, and although some hydration of the contents was evident, erosion of the tablet plug is most probably the controlling factor in timed release. The premature failure of the aqueous-coated capsule appears to be a result of rapid influx of water between plug and capsule with hydration of the low substituted hydroxypropylcellulose expulsion agent. As a result of this, the tablet plug remains intact, but appears unable to be ejected. The resulting significant pressure build-up causes premature release by distortion and splitting of the capsule shell. These events may be aided by a weakening of the aqueous-coated gelatin shell by hydration from the inside, and at the mouth of the capsule where previous electron microscope studies have shown incomplete coating of the inside by the aqueous process.

Topics: Calcium Phosphates; Capsules; Carboxymethylcellulose Sodium; Cellulose; Delayed-Action Preparations; Drug Delivery Systems; Excipients; Image Processing, Computer-Assisted; Kinetics; Lactose; Magnetic Resonance Imaging; Propranolol; Solvents; Spectrophotometry, Ultraviolet; Stearic Acids; Water

Topics: Animals; Cellulose; Cysteamine; Cysteine; Delayed-Action Preparations; Radiation Injuries, Experimental; Radiation-Protective Agents; Rats; Rats, Inbred Lew; Stearic Acids; Tablets