Clofibrate Microcapsules: III. Mechanism of Release

Abstract

The mechanism of release of clofibrate from microcapsules prepared in a gelatin-sodium sulfate system has been investigated. A theoretical model was developed to explain the release pattern of the drug from the microcapsules. It was shown that the release of the drug followed four stages giving individual zero-order profiles. The overall release from the thin-walled microcapsules showed greater deviation from the zero-order kinetics but followed the square-root of the time plots. Microcapsules having thicker walla approximated overall zero-order release but deviated from the square-root of time plots. The effect of hardening on the release profiles and possible explanations for the differences observed in the release of clofibrate from the thin-walled and thick-walled microcapsules are discussed.     

Optimization of Slow-Release Tablet Formulations Containing Montmorillonite III. Mechanism of Release

The release of sodium sulfathiazole from slow-release tablet dosage forms containing 30% colloidal aluminum silicate and 20% drug, appears to follow first-order kinetics. Analysis of the data however, suggests that several mechanisms including hydration of the clay, diffusion of drug through a hydrated gelatinous barrier and attrition of the gel layer may contribute to the dissolution of sodium sulfathiazole from the tablet matrix. The influence of tablet shape and size on the dissolution properties of drug from the dosage forms was also examined.     

Controlled Release Kinetics of Captopril From Tableted Microcapsules

Abstract

Different viscosity grades ethylcellulose coated captopril microcapsules were prepared using temperature induced coacervation method from cyclohexane containing 2% Tween 80. Microcapsules were compressed directly into tablets. In vitro dissolution was carried out in 0.1 N HCl at 37°C using the rotating basket method. Release from tablets of all the batches was extensively prolonged in comparison to the respective microcapsules. The longest time for 70% drug release was shown by microcapsules (55min) and tablets (378 min) of the batch E-2. Release rate constants, correlation, determination and regression coefficients were calculated for the first-order, zero-order and Higuchi's equations. The best fit of release kinetics with the highest correlation and determination coefficients was achieved with the first-order followed by Higuchi's plot.     

Compression of Microcapsules I: Effect of Excipients and Pressure on Drug Release

Abstract

Microcapsules containing phenylpropanolamine-resin complexes were compressed with various diluents. Compression of microcapsules produced an increase in the release rate. An average reduction of 0.50 hours was observed when Emdex or Fast Flo Lactose were compared to Avicel at various pressures (35 to 281 MPa). Increasing the amount of microcapsules in the formulation reduced the T50% with all three diluents     

Compression of Microcapsules I: Effect of Excipients and Pressure on Drug Release

Microcapsules containing phenylpropanolamine-resin complexes were compressed with various diluents. Compression of microcapsules produced an increase in the release rate. An average reduction of 0.50 hours was observed when Emdex or Fast Flo Lactose were compared to Avicel at various pressures (35 to 281 MPa). Increasing the amount of microcapsules in the formulation reduced the T50% with all three diluents     

异噻唑啉酮微胶囊的制备表征及释放行为

以二异氰酸酯(TDI)、聚乙二醇4000(PEG)、二羟甲基丙酸(DMPA)和三乙胺(TEA)为原料,制备可水乳化的聚氨酯(WPU).以合成的WPU为囊壁、以异噻唑啉酮衍生物(Sea-nine 211)为囊芯,通过乳化自组装得到防污剂Sea-nine 211微胶囊,用红外光谱、粒径分布和扫描电镜对胶囊进行表征,并采用分...     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^-2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

甜玉米芯多糖纳米乳微胶囊制备及释放

目的 改善甜玉米芯多糖(SCP)大分子特性以及稳定性,促进SCP的肠道吸收。方法 将SCP水溶液制备成油包水型(W/O)甜玉米芯多糖纳米乳液(SCP-NE),以复合蛋白为壁材制备成SCP-NE微胶囊,采用单因素试验、Box-Behnken设计和响应面法优化SCP-NE微胶囊制备工艺,以粒径分析、红外光谱分析、热重分析,对SCP-NE微胶囊物化性质进行研究,并进行体外模拟胃肠液释放研究。结果 制备SCP-NE微胶囊最佳条件为麦芽糊精(MD)与大豆分离蛋白(SPI)的质量比为2∶3、芯壁比为1∶2、总体固形物含量为20%,此时包封率达到(87.6±1.3)%。体外模拟胃肠液释放结果表明,SCP-NE微胶囊在2 h的胃液消化中释放率为8.83%,在模拟肠液中1 h的释放量为62.87%。结论 以MD和SPI作为壁材制备的SCP-NE微胶囊在胃肠液释放中具有良好的缓释性能。     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Abstract

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^?2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Medicament Release from Ointment Bases: III. Ibuprofen: In Vitro Release and In-Vivo Absorption in Rabbits

Abstract

The in-vitro release of ibuprofen from various topical bases including: water-washable base, hydrophilic base, cream, Canadian formulary base, gel, emulsion, water-soluble base and University of California Hospital base were studied. Also, the effects of the additives (ethanol, polyethylene glycol—400, urea and dimethylsulfoxide) on the release rate of the drug from the water-washable base were evaluated.

In general, the in-vitro release rate rank order of the drug was observed to be: water-washable base > hydrophilic base > Canadian formulary base > gel > PEG water washable > emulsion > cream > University of California base. The additive ingredients had a Little or no effect in enhancing the release of drug from the samples studied.

The formulations with optimum in-vitro drug release were scaled up for in-vivo percutaneous absorption in rabbits. The blood samples were analyzed by a HPLC method. Among the candidates evaluated in-vivo, the bioavailability of the drug was significantly higher from the water-washable base when compared to the hydrophilic base and others. The addition of 10% dimethylsulfoxide to the hydrophilic enhanced the release of ibuprofen and adversely affected the release from the water-washable base.

In-vitro and in-vivo data were treated by various kinetic models and the values for diffusion coefficient, permeability coefficient and partition coefficient were calculated. Also, some pharmacokinetic parameters, such as, absorption rate constant, elimination rate constant and half-life of the drug were calculated for meaningful interpretations of the data for the release of drug from topical bases.     

Microfluidic Production of Biodegradable Microcapsules for Sustained Release of Hydrophilic Actives

Biodegradable microcapsules with a large aqueous lumen and ultrathin membrane are microfluidically designed for sustained release of hydrophilic bioactives using water‐in‐oil‐in‐water double‐emulsion drops as a template. As a shell phase, an organic solution of poly(lactic‐co‐glycolic acid) is used, which is consolidated to form a biodegradable membrane. The encapsulants stored in the lumen are released over a long period of time as the membranes degrade. The period can be controlled in a range of —three to five months at neutral pH condition by adjusting membrane thickness, providing highly sustained release and potentially enabling the programed release of multiple drugs. At acidic or basic condition, the degradation is accelerated, leading to the release in the period of approximately two months. As the membrane is semipermeable, the microcapsules respond to the osmotic pressure difference across the membrane. The microcapsules are inflated in hypotonic condition and deflated in hypertonic condition. Both conditions cause cracks on the membrane, resulting in the fast release of encapsulants in a day. The microcapsules implanted in mice also show sustained release, despite the period is decreased to a month. It is believed that the microcapsules are promising for the in vivo sustained release of drugs for high and long‐term efficacy.     

25th Anniversary Article: Double Emulsion Templated Solid Microcapsules: Mechanics And Controlled Release

How droplet microfluidics can be used to fabricate solid‐shelled microcapsules having precisely controlled release behavior is described. Glass capillary devices enable the production of monodisperse double emulsion drops, which can then be used as templates for microcapsule formation. The exquisite control afforded by microfluidics can be used to tune the compositions and geometrical characteristics of the microcapsules with exceptional precision. The use of this approach to fabricate microcapsules that only release their contents when exposed to a specific stimulus – such as a change in temperature, exposure to light, a change in the chemical environment, or an external stress – only after a prescribed time delay, and at a prescribed rate is reviewed.     

Controllable Fabrication of Inhomogeneous Microcapsules for Triggered Release by Osmotic Pressure

Inhomogeneous microcapsules that can encapsulate various cargo for controlled release triggered by osmotic shock are designed and reported. The microcapsules are fabricated using a microfluidic approach and the inhomogeneity of shell thickness in the microcapsules can be controlled by tuning the flow rate ratio of the middle phase to the inner phase. This study demonstrates the swelling of these inhomogeneous microcapsules begins at the thinnest part of shell and eventually leads to rupture at the weak spot with a low osmotic pressure. Systematic studies indicate the rupture fraction of these microcapsules increases with increasing inhomogeneity, while the rupture osmotic pressure decreases linearly with increasing inhomogeneity. The inhomogeneous microcapsules are demonstrated to be impermeable to small probe molecules, which enables long‐term storage. Thus, these microcapsules can be used for long‐term storage of enzymes, which can be controllably released through osmotic shock without impairing their biological activity. The study provides a new approach to design effective carriers to encapsulate biomolecules and release them on‐demand upon applying osmotic shock.     

Controlled Nifedipine Release from Microcapsules of its Dispersions in PVP-MCC and HPC-MCC

Nifedipine and its solid dispersions in polyvinyl-pyrrolidone-microcrystalline cellulose (PVP-MCC) and hydroxypropyl cellulose - microcrystalline cellulose (HPC-MCC) were microencapsulated with cellulose acetate by an emulsion solvent evaporation method. The microcapsules are spherical, discrete and free flowing. Nifedipine as such and its microcapsules gave very slow release because of its highly crystalline nature and poor solubility. Solid dispersion in PVP-MCC and HPC-MCC gave fast and rapid dissolution of nifedipine. When these solid dispersions were microencapsulated, a slow, controlled and complete release over a period of 12 hours was observed from the resulting microcapsules. Drug release depended on the proportion of PVP-MCC and HPC-MCC in the solid dispersions used as core, coat: core ratio and size of the microcapsules and the release was pH independent. Drug release was governed by diffusion rate and followed first-order kinetics.     

Eudragit Microcapsules of Nifedipine and Its Dispersions in HPMC-MCC: Physicochemical Characterization and Drug Release Studies

Nifedipine and its solid dispersions in hydroxypropyl methyl cellulose-microcrystalline cellulose (HPMC-MCC) were microencapsulated with Eudragit RL PM by an emulsion solvent evaporation method. The microcapsules are spherical, discrete, free flowing, and covered with a continuous coating of the polymer. XRD and DTA indicated the presence of nifedipine in solution form in the solid dispersions and their microcapsules. No chemical interaction between nifedipine and excipients in the microcapsules was observed. Nifedipine as such and its microcapsules gave very slow release because of its highly crystalline nature and poor solubility. Solid dispersion in HPMC-MCC gave fast and rapid dissolution of nifedipine. When these solid dispersions were microencapsulated a slow, controlled, and complete release over a period of 12 hr was observed from the resulting microcapsules. Drug release depended on the proportion of HPMC-MCC in the solid dispersion used as a core, coat, core ratio, and size of the microcapsules. Release was independent of pH and ionic strength. Drug release was governed by diffusion rate and followed first-order kinetics.     

Eudragit Microcapsules of Nifedipine and Its Dispersions in HPMC-MCC: Physicochemical Characterization and Drug Release Studies

Abstract

Nifedipine and its solid dispersions in hydroxypropyl methyl cellulose-microcrystalline cellulose (HPMC-MCC) were microencapsulated with Eudragit RL PM by an emulsion solvent evaporation method. The microcapsules are spherical, discrete, free flowing, and covered with a continuous coating of the polymer. XRD and DTA indicated the presence of nifedipine in solution form in the solid dispersions and their microcapsules. No chemical interaction between nifedipine and excipients in the microcapsules was observed. Nifedipine as such and its microcapsules gave very slow release because of its highly crystalline nature and poor solubility. Solid dispersion in HPMC-MCC gave fast and rapid dissolution of nifedipine. When these solid dispersions were microencapsulated a slow, controlled, and complete release over a period of 12 hr was observed from the resulting microcapsules. Drug release depended on the proportion of HPMC-MCC in the solid dispersion used as a core, coat, core ratio, and size of the microcapsules. Release was independent of pH and ionic strength. Drug release was governed by diffusion rate and followed first-order kinetics.     

基于灰色理论的中空海藻酸钠微胶囊释药模型研究

以阿维菌素（AVM）为模型药物,制备了一种中空海藻酸钠（SA）微胶囊。应用灰色系统理论GM（1,1）模型对中空SA微胶囊的缓释性能进行了模拟预测。模型的模拟预测值与实验数据的相对误差较小,表明灰色系统理论可用于模拟和预测中空SA微胶囊的药物释放行为。     

Controlled Theophylline Release from Microcapsules of Acrylic & Methacrylic Acid Ester Copolymer

The goal of this work was to develop a suitable method for microencapsulation of theophylline using copolymer of acrylate and methacrylate ester (EUDRAGIT) as the coating material. The effect of protective colloids on the process of microencapsulation was evaluated. The in vitro studies revealed significant control of drug release for the developed dosage form. Individually, the polymer coated drug particles of different core: coat ratio and different proportions of protective colloids were found to influence the pharmacokinetic parameters as revealed from the in vivo bioavailability studies in gastric-emptying controlled rabbits. In vivo bioavailability data were compared using Westlake's confidence limit.