Evaluation of a Microreservoir-Type Biodegradable Microcapsule for Controlled Release of Proteins

For the controlled release of a model protein bovine serum albumin, a biodegradable microreservoir-type microcapsule was prepared. BSA was incorporated into the microcapsules with high efficiency of 96.1 (±3.1)%. The encapsulation did not cause any changes in the molecular weight and conformation of BSA, which was proven by biochemical analyses such as gel electrophoresis, circular dichroism, and HPLC.

The compositions and fabrication technique of microcapsules were found to be closely related to the release of BSA from the microcapsules and their degradation. Depending on microcapsule formulations, the in vitro release profile of BSA was either monophasic or biphasic. The microcapsules provided various release rates. It was also possible to control the delay before the initiation of BSA release and total duration of its delivery.     

Development of Biodegradable and Injectable Latices for Controlled Release of Potent Drugs

A new dosage form designed to provide parenteral drug delivery over a prolonged period of time following a standard injection has been investigated using testosterone as the model drug. The drug carrier consists of a biodegradable, biocompatible polymer in which the drug is dispersed on a molecular level. The polymer itself is formulated as a pseudolatex with high solid content (40.0%). The formulation has a low viscosity (97 cps) which can be injected easily through a hypodermic needle. The histopathology study showed good tissue compatibility of the pseudolatices and in-vivo tests on rats confirmed a prolonged release of drug over a 14 day period. The stability of the biodegradable poly-d, l-lactic acid latex was found not to be significantly changed over 120 days of storage at room temperature (25°). A six month study showed a slight increase (10%) in the viscosity of the parenteral product when stored at room temperature. The increase was attributed to partial coalescence of the polymer particles which had an initial diameter of 0.45 μm.     

聚乳酸类可生物降解材料在缓控释药物制剂中的应用

综述了用聚乳酸类可生物降解型高分子材料制备缓控释药物载体的研究现状.分别介绍了该类材料在微粒给药载体、凝胶制剂、缓释支架和埋植制剂的应用及其制备方法.阐述了目前聚乳酸类生物降解材料在缓控释药物制剂中的主要问题,展望了其发展前景.     

Evaluation of Spray-Drying as a Method to Prepare Microparticles for Controlled Drug Release

The possibility to obtain microcapsules or microspheres for controlled release by spray-drying is evaluated. Drugs of different solubilities like theophylline and sodium sulfamethazine, with Eudragit RS as coating polymer, are chosen.

The polymer is used, either dissolved in an hydroalcoholic solution or suspended (pseudolatex) in water, in different weight ratios with the drug. The obtained solution or suspension is spray-dried.

Scanning electron microscope analysis of the powders reveals no sign of microencapsulation. Moreover, only a fraction of the particles has a spherical shape.

For each spray-dried powder, a part of the obtained particles is compressed into tablets, and the rest is stored.

Dissolution studies in distilled water at 37 C are performed on powders and tablets.

While the uncompressed microparticles do not give any controlled release, the tablets show an ability in slowing down drug delivery greater than the one obtained with the traditional methods.     

Simple Evaluation Method of Intrinsic Diffusivity for Membrane-Moderated Controlled Release

The effect of diffusion boundary layers in an in vitro membrane permeation system on the membrane diffusivity of drugs was investigated based on the three-layer model. A simple method for evaluating the intrinsic diffusivity through the membrane was developed and the intrinsic diffusivity of progesterone and testosterone through a silicone membrane were determined using this approach.     

Evaluation of Spray-Drying as a Method to Prepare Microparticles for Controlled Drug Release

The possibility to obtain microcapsules or microspheres for controlled release by spray-drying is evaluated. Drugs of different solubilities like theophylline and sodium sulfamethazine, with Eudragit RS as coating polymer, are chosen.

The polymer is used, either dissolved in an hydroalcoholic solution or suspended (pseudolatex) in water, in different weight ratios with the drug. The obtained solution or suspension is spray-dried.

Scanning electron microscope analysis of the powders reveals no sign of microencapsulation. Moreover, only a fraction of the particles has a spherical shape.

For each spray-dried powder, a part of the obtained particles is compressed into tablets, and the rest is stored.

Dissolution studies in distilled water at 37 C are performed on powders and tablets.

While the uncompressed microparticles do not give any controlled release, the tablets show an ability in slowing down drug delivery greater than the one obtained with the traditional methods.     

Simple Evaluation Method of Intrinsic Diffusivity for Membrane-Moderated Controlled Release

Abstract

The effect of diffusion boundary layers in an in vitro membrane permeation system on the membrane diffusivity of drugs was investigated based on the three-layer model. A simple method for evaluating the intrinsic diffusivity through the membrane was developed and the intrinsic diffusivity of progesterone and testosterone through a silicone membrane were determined using this approach.     

Preparation and Evaluation of Controlled Release Indomethacin Microspheres

Microspheres containing indomethacin were prepared with various combinations of polymers Eudragit RS and Eudragit L. The effects of different ratios of polymers, solvent-polymer ratio, polymer-drug ratio and evaporation temperature on the physical characteristics of the microspheres as well as the in vitro release rate of the drug were investigated. All the factors studied had an influence on the physical characteristics of the microspheres. In vitro dissolution results showed that all formulations gave prolonged release of indomethacin and the release followed apparent zero order kinetics until 80% of drug had been released.     

Preparation and Evaluation of Controlled Release Indomethacin Microspheres

Abstract

Microspheres containing indomethacin were prepared with various combinations of polymers Eudragit RS and Eudragit L. The effects of different ratios of polymers, solvent-polymer ratio, polymer-drug ratio and evaporation temperature on the physical characteristics of the microspheres as well as the in vitro release rate of the drug were investigated. All the factors studied had an influence on the physical characteristics of the microspheres. In vitro dissolution results showed that all formulations gave prolonged release of indomethacin and the release followed apparent zero order kinetics until 80% of drug had been released.     

High-Throughput Evaluation of Non-Swellable Controlled Release Matrix Tablets

Abstract

Drug release from controlled-release (CR) matrix tablets involves the permeation and diffusion of water through the system. In this study, a new methodology is proposed for the measurement of water permeation and simultaneous drug release from the inert, non-swellable CR matrix tablet of diltiazem (DLT) and a correlation is made between these two processes. Cylindrical matrices were readily prepared by direct compression of pellets obtained by extrusion-spheronization. Water transport was studied using tritiated water (HTO) as a permeant in a Franz-diffusion cell and simultaneously drug release was measured. Further, dissolution was performed on USP XXI/XXII dissolution apparatus I using demineralized water. Matrices showed a steady water-uptake up to 6 h and the steady state for HTO permeation lasting from 6-h to 24-h Flux of water permeated and flux of drug released correlated well. Thus, HTO permeation through the matrix tablet and the proposed methodology can be used as a tool and/or surrogate marker for evaluation of controlled release matrix tablets. This methodology can be coined as “high-throughput” in terms of amount of labor and resources required in comparison to that of dissolution.     

Preparation and Evaluation of Controlled Release Propranolol Hydrochloride Beads

Abstract

Conventional pan coating method was utilized to prepare propranolol-HCl sustained release coated beads. Eudragit RS 100 was used as release controlling materials. Overcoating of the beads with beeswax was also investigated. The beads were characterized for their particle size distribution, drug loading efficiency and their dissolution behaviour in 0.1N HCl, Most of the finished beads (72.4%) fall in the particle size range 800–1700 um. The actual drug content, calcu-lated as opposed to the theoretical drug content were 77.6% and 74.2% of the drug for the beads having particle size range 1700–1250 um and 1250–800 um respectively, The coating level of the polymer, the particle size of the beads and overcoating with beeswax play a major role in determining the release rate of the drug from the coated beads.     

Preparation and Evaluation of Controlled Release Propranolol Hydrochloride Beads

Conventional pan coating method was utilized to prepare propranolol-HCl sustained release coated beads. Eudragit RS 100 was used as release controlling materials. Overcoating of the beads with beeswax was also investigated. The beads were characterized for their particle size distribution, drug loading efficiency and their dissolution behaviour in 0.1N HCl, Most of the finished beads (72.4%) fall in the particle size range 800-1700 um. The actual drug content, calcu-lated as opposed to the theoretical drug content were 77.6% and 74.2% of the drug for the beads having particle size range 1700-1250 um and 1250-800 um respectively, The coating level of the polymer, the particle size of the beads and overcoating with beeswax play a major role in determining the release rate of the drug from the coated beads.     

壳聚糖/PHB复合缓释微包囊的制备与体外释药评价

用疏水性聚酯PHB外包覆壳聚糖-三聚磷酸钠-阿斯匹林药物缓释体(CPA)制备了壳聚糖/PHB复合缓释微包囊(CPAB),以克服CPA遇酸不稳定的释药特点.用傅立叶红外分光光度计、激光粒度仪、扫描电镜表征了CPAB的组成、粒径及表面形貌.结果显示,CPAB粒径在50～100nm和载药率18.5%时,表面有不均匀的空隙.体外释药评价证实CPAB能有效解决CPA在酸性下的不稳定性,具有长效缓释作用.     

Development and In-Vitro Evaluation of Ethyl Cellulose Micropellets as a Controlled Release Dosage Form for Theophylline

Abstract

A micropellet dosage form was developed using ethyl cellulose as a polymer with a view to achieve a controlled release oral drug delivery system for theophylline. Drugpolymer ratios and stirring speeds were found to influence the size-distribution of micropellets. Time required for 50% release of theophylline from micropellets was found to vary linearly with the drug content and reciprocal of diameter of micropellets. Invitro release of theophylline from micropellets, having different drug-polymer ratios and different sizes, was found apparently to follow both the First-order release and Diffusion controlled release processes. By differential rate treatment it was found that the overall release, in fact, followed diffusion controlled process.     

Development and In-Vitro Evaluation of Ethyl Cellulose Micropellets as a Controlled Release Dosage Form for Theophylline

A micropellet dosage form was developed using ethyl cellulose as a polymer with a view to achieve a controlled release oral drug delivery system for theophylline. Drugpolymer ratios and stirring speeds were found to influence the size-distribution of micropellets. Time required for 50% release of theophylline from micropellets was found to vary linearly with the drug content and reciprocal of diameter of micropellets. Invitro release of theophylline from micropellets, having different drug-polymer ratios and different sizes, was found apparently to follow both the First-order release and Diffusion controlled release processes. By differential rate treatment it was found that the overall release, in fact, followed diffusion controlled process.     

Design and in Vitro Evaluation of a Controlled Release Drug Delivery System of Sulfasomidine

Abstract

A controlled release oral drug delivery system of Sulfasomidine was developed by spray congealing micropelleting technique using gelatin as the embedding matrix. The pellets were hardened by treating with Formalin-Isopropanol mixture. The in vitro release rate studies of Sulfasomidine from the micropelleted dosage form, revealed that the drug release can be prolonged upto eight hours and not more than 39% of the embedded drug released in the first hour of the in vitro dissolution study. The in vitro release patterns correlated with the reported in vivo studies. The method of formulation was optimized.     

Design and in Vitro Evaluation of a Controlled Release Drug Delivery System of Sulfasomidine

A controlled release oral drug delivery system of Sulfasomidine was developed by spray congealing micropelleting technique using gelatin as the embedding matrix. The pellets were hardened by treating with Formalin-Isopropanol mixture. The in vitro release rate studies of Sulfasomidine from the micropelleted dosage form, revealed that the drug release can be prolonged upto eight hours and not more than 39% of the embedded drug released in the first hour of the in vitro dissolution study. The in vitro release patterns correlated with the reported in vivo studies. The method of formulation was optimized.     

Evaluation of Chitosan Citrate Complexes as Matrices for Controlled Release Formulations Using a 32 full Factorial Design

Chitosan citrate complexes of several viscocity grades were synthesized, isolated, purified and identified. These complexes were found to form viscous gels of varying viscosities, upon dispersion in water. The ability of these complexes in sustaining drug release from matrix tablets was evaluated using a two factor three level full factorial design with theophylline as the model drug. Viscosity and concentration of the polymer complexes were optimized to achieve the desired in-vitro release profile. In-vitro dissolution characteristics were evaluated in deionized water as the dissolution medium. Data were fit to a quadratic model and polynomial equations were generated and used to predict the optimum formulation composition with desired release characteristics. These complexes were found to be very effective in sustaining the release of theophylline and were directly compressible. The release mechanism appears to be diffusion controlled. Excellent correlation was obtained between predicted and actual release profiles of the optimum formula.     

Evaluation of Chitosan Citrate Complexes as Matrices for Controlled Release Formulations Using a 32 full Factorial Design

Abstract

Chitosan citrate complexes of several viscocity grades were synthesized, isolated, purified and identified. These complexes were found to form viscous gels of varying viscosities, upon dispersion in water. The ability of these complexes in sustaining drug release from matrix tablets was evaluated using a two factor three level full factorial design with theophylline as the model drug. Viscosity and concentration of the polymer complexes were optimized to achieve the desired in-vitro release profile. In-vitro dissolution characteristics were evaluated in deionized water as the dissolution medium. Data were fit to a quadratic model and polynomial equations were generated and used to predict the optimum formulation composition with desired release characteristics. These complexes were found to be very effective in sustaining the release of theophylline and were directly compressible. The release mechanism appears to be diffusion controlled. Excellent correlation was obtained between predicted and actual release profiles of the optimum formula.