克拉霉素微囊的制备及其质量评价

目的:制备克拉霉素微囊并对其质量进行评价。方法:以乙基纤维素为囊材,采用乳化-溶剂挥发法制备克拉霉素微囊,并对微囊粒径、包封率和载药量、体外释药性进行考察。结果:所制微囊粒径分布均匀,粒径33.0～38.0μm,包封率在87%以上,载药量大于45%,6h时累积释药量达75%。结论:该制剂制备方法简便易行,质量评价合格。     

对乙酰氨基酚复合微囊缓释栓的制备及体外释放度研究

目的:采用复凝聚法制备对乙酰氨基酚(AAP)微囊并考察其体外释药行为。制备AAP复合微囊栓剂,具有良好释放效果。方法:考察复凝聚法制备AAP微囊过程的处方和工艺因素,并进行正交试验设计,筛选出最佳条件制备AAP微囊并考察其体外释药行为。同时采用复合缓释技术(速释部分+微囊缓释)制备复合微囊缓释栓剂,考察其释药行为。结果:建立了复凝聚法制备AAP微囊方法,优化后的制备条件为:明胶阿拉伯胶囊材用量各为7 g(溶液浓度7%),药物用量为8 g,搅拌速度为300 r·min^-1,制备温度55℃。此条件制备的微囊形态圆整,粒径均匀,重复性好,包封率为(79.71±0.10)%,载药量为23.11±0.69%。微囊有缓释效果,拟合缓释方程符合一级方程。制备的复合微囊栓与普通栓剂相比,具有更好的释放效果,其中缓释过程药物释放符合Higuchi方程。结论:基于普通栓剂与复合微囊技术制备的新型AAP栓具有更佳的释药特性。     

乳化溶剂挥发法制备重组人血管内皮抑制素缓释微球

目的:制备重组人血管内皮抑制素(恩度)缓释微球,并对微球理化性质及体外释放行为进行初步考察。方法:采用乳化溶剂挥发法(W/O/O)制备恩度载药微球;对微球载药量、粒径、突释、体外释放速率及降解行为进行考察,同时利用凝胶电泳初步评价体外释放过程中恩度的完整性。结果:增加聚乳酸-羟基乙酸嵌段共聚物(PLGA)中羟基乙酸的比例、提高PLGA浓度、降低内水相体积、提高理论载药量均增加微球载药能力;降低内水相体积、提高分散速度均减小突释。增加PLGA中羟基乙酸的比例,30 d时累积释放可增加到65%。降解实验说明释放初期微球主要以扩散方式释放恩度,释放后期主要表现为微球的降解。凝胶电泳结果表明微球制备过程对蛋白质聚集性的影响不大。结论:用PLGA作为载体材料制备微球,可以延缓恩度的释放。     

正交实验设计优化岩白菜素微囊的制备工艺

目的优化岩白菜素微囊的制备工艺,并对制备的岩白菜素微囊进行质量评价。方法以明胶为囊材,单凝聚法制备岩白菜素微囊,通过正交实验设计优化其制备工艺,并对包封率、载药量、平均粒径、体外溶出率进行研究。结果明胶制备岩白菜素微囊的最佳工艺条件为:明胶质量分数为6%,囊心囊材质量比为1∶2,搅拌速度为750r·min^-1。此最佳工艺制备的岩白菜素微囊包封率为75.90%,载药量为23.09%,体外溶出度测定30min为28.6%,12h累计释放达到90%以上。结论以最佳工艺条件制备岩白菜素微囊工艺稳定,包封率高,同时体外释放实验表明,该微囊具有较好的缓释作用。     

更昔洛韦肺部靶向微囊的制备及体外释放度测定

目的:制备更昔洛韦肺部靶向微囊并测定其体外释放度。方法:以双乳化溶剂挥发法制备微囊;采用紫外分光光度法测定微囊的体外释药量,考察其体外释放度。结果:所制微囊外观圆整,平均粒径13.87μm;更昔洛韦检测浓度的线性范围为2～20μg·mL-1(r=0.999 9),平均回收率为99.96%(RSD=1.68%);包封率为63.85%,24h累积体外释放度约为40%。结论:更昔洛韦肺部靶向微囊具有良好的缓释性。     

盐酸小檗碱微囊的制备及其体外释放研究

目的:为改善口感、减小对胃黏膜的刺激,制备盐酸小檗碱微囊,并考察其体外释药特性。方法:以阿拉伯胶、明胶为囊材,采用复凝聚法制备盐酸小檗碱微囊,以包封率、载药量、外形为指标,采用正交设计试验对囊心(盐酸小檗碱)-囊材质量比、囊材质量分数、搅拌速度进行优化,并进行验证。考察所制制剂的粒径分布及在人工肠液中5 h内的体外释药率。结果:最优处方为囊心-囊材质量比为1∶3,阿拉伯胶和明胶的质量分数均为2.50%,搅拌速度为200 r/min,成囊温度为53℃。所制盐酸小檗碱微囊的包封率为38%,载药量为41.71%;微囊圆整光滑,无粘连,粒径均匀,外形评分50.6;80%以上分布在3~9μm;3 h的累积释药率即达90%。结论:成功制得盐酸小檗碱微囊。     

酮咯酸氨丁三醇海藻酸钠-壳聚糖微囊的制备

以微囊的载药量和包封率为指标,采用均匀设计,结合非线性规划法优化酮咯酸氨丁三醇海藻酸钠-壳聚糖微囊的制备工艺.结果表明,按优化条件制得的微囊包封率90%,载药量44%,在水中的释药行为符合Higuchi方程.     

处方和工艺参数对盐酸昂丹司琼微球体外释放度的影响

目的：考察处方工艺参数对微球体外释放度的影响.方法：采用O/O型乳化溶剂挥发法,以乳酸-羟基乙酸共聚物为载体,制备盐酸昂丹司琼（Ondansetron hydrochloride,OND）微球.采用紫外分光光度法测定微球的体外释放度.结果：选择对OND具有较好溶解能力的混合溶剂为内油相溶剂,可以降低突释;增加理论载药量,延缓正己烷加入的时间和减小粒径可以增加OND微球的释药速度.结论：通过对处方和工艺的调节可使OND微球的体外释药曲线符合Higuchi方程,2周的累积释放量在80%左右.     

难溶性药物布洛芬药物树脂复合物的制备及其体外释放研究

目的:制备布洛芬药物树脂复合物,并考察其体外释药动力学。方法:将布洛芬制备成可溶性的钠盐,采用不同交联度的离子交换树脂为载体以静态法制备布洛芬树脂复合物,并对布洛芬树脂复合物释放的影响因素进行考察。结果:随着树脂交联度的减小,树脂对布洛芬的载药速率变快,载药量增加。体外释药动力学研究表明,布洛芬药物树脂的释药速率随着释放介质离子强度的增加,温度的升高,以及树脂交联度和粒径的减小而加快;且布洛芬药物树脂的释放为pH依赖型。结论:采用离子交换树脂为载体制备的布洛芬树脂复合物具有一定的缓释特征。     

白藜芦醇PLGA长效注射微球的制备及工艺考察

目的采用乳化溶剂挥发法制备白藜芦醇聚乳酸羟基乙酸[poly(lactic-co-glycolic acid),PL-GA]长效微球,评价各因素对微球性质的影响。方法以微球的包封率、载药量、突释和粒径作为微球的质量评价指标,研究分散相与连续相的体积比、PLGA浓度、聚乙烯醇(polyvinyl alcohol,PVA)浓度、搅拌速度对微球性质的影响,并优化白藜芦醇PLGA微球的制备工艺。结果分散相与连续相的体积比为1∶50时,包封率高,但4 h突释量达到76%,当分散相与连续相体积比由1∶50提升到1∶150时,突释降低了22%;随着聚合物浓度的增加粒径明显增大,突释显著降低;理论载药量对粒径影响不大,在高载药量时突释显著减少;搅拌速度的增加使粒径减小,突释增加;PVA浓度的增加对粒径没有明显的影响,但当PVA的质量浓度从1 g.L-1增加到5 g.L-1时,包封率从93.57%降低到80.31%。结论分散相与连续相的体积比、PLGA浓度、PVA浓度、搅拌速度对微球性质有很大的影响。优化条件下制备的微球形态完整,载药量为(27.86±1.00)%,包封率为(93.57±2.87)%,平均粒径约为21.12μm。白藜芦醇PLGA微球体外释放25 d的累积释药率达(94.04±4.94)%,有望研制成1个月给药1次的给药系统。     

Effect of viscosity and concentration of wall former, emulsifier and pore-inducer on the properties of amoxicillin microcapsules prepared by emulsion solvent evaporation

This study reports the laboratory optimization for the preparation of sustained release amoxicillin (AMX) ethylcellulose microcapsules by an emulsion solvent evaporation process by adjusting the viscosity and concentration of ethylcellulose, ratio of amoxicillin to ethylcellulose, and concentration of emulsifier and pore inducer. When ethylcellulose with a viscosity of 45 mPa.s was used, almost no material stuck to the inside wall of the beaker and uniform microcapsules were prepared. The average diameter of microcapsules increased and yield and release rate decreased as the concentration of ethylcellulose increased from 1% to 8%. The release of amoxicillin from microcapsules was influenced by the ratio of the weight of drug to that of ethylcellulose and ratios of 2:1 and 4:1 were most suited for optimum amoxicillin release. The average diameter of microcapsules decreased and the release rate increased as the concentration of the emulsifier increased from 1.5% to 6.0%, however, the size distribution became significantly wider with the increase in the concentration of sorbitan monooleate. Addition of small amounts of a water-soluble agent sucrose improved the release of active ingredient from the microcapsule matrix without influencing the morphology and particulate properties of the microcapsules.     

Preparation and evaluation of ethylcellulose microcapsules of indomethacin

Indomethacin was microencapsulated with ethylcellulose using a modified spherical agglomeration process, aiming at a sustained release preparation without side effects on the stomach. The surface morphology of the microcapsules was examined using scanning electron microscopy. The microcapsules were porous and spherical, and their porosity increased with increasing the viscosity of ethylcellulose.In vitro dissolution process followed Higuchi’s diffusion model for first 3 hr. Release rate of the drug from microcapsules decreased as the viscosity of ethylcellulose or the weight ratio of indomethacin to ethylcellulose was decreased. The release rate also decreased with increasing the microcapsule size. The microcapsules induced less gastric ulcer in rats than raw drug.     

An enhanced process for encapsulating aspirin in ethyl cellulose microcapsules by solvent evaporation in an O/W emulsion

An enhanced process for microencapsulating aspirin in ethylcellulose was demonstrated using an oil-in-water emulsification/solvent evaporation technique. Methylene chloride (CH2Cl2) was used as the dispersed medium and water as the dispersing medium. The recovered weight, particle size distribution, aspirin loading efficiency, and the aspirin release rate of microcapsules were analysed. The addition of appropriate amounts of non-solvent (n-heptane) prior to the emulsification increases the recovered weight, but decreases the size of the formed microcapsules. The addition of non-solvent also changes the microcapsule characteristics, resulting in a coarser surface and an increased release rate. Increasing the polymer (ethylcellulose) concentration in the dispersed phase increases the size of the microcapsules, the recovered weight, and loading efficiency, but decreases the release rate. The release rate follows first-order kinetics during the first 12 h, suggesting a monolithic system with aspirin uniformly distributed in the microcapsule.     

An enhanced process for encapsulating aspirin in ethyl cellulose microcapsules by solvent evaporation in an O/W emulsion

An enhanced process for microencapsulating aspirin in ethylcellulose was demonstrated using an oil-in-water emulsification/solvent evaporation technique. Methylene chloride (CH2Cl2) was used as the dispersed medium and water as the dispersing medium. The recovered weight, particle size distribution, aspirin loading efficiency, and the aspirin release rate of microcapsules were analysed. The addition of appropriate amounts of non-solvent (n-heptane) prior to the emulsification increases the recovered weight, but decreases the size of the formed microcapsules. The addition of non-solvent also changes the microcapsule characteristics, resulting in a coarser surface and an increased release rate. Increasing the polymer (ethylcellulose) concentration in the dispersed phase increases the size of the microcapsules, the recovered weight, and loading efficiency, but decreases the release rate. The release rate follows first-order kinetics during the first 12h, suggesting a monolithic system with aspirin uniformly distributed in the microcapsule.     

Preparation and in vitro evaluation of polylactic acid-mitomycin C microcapsules

Abstract

An emulsion method was developed for the incorporation of water-soluble mitomycin C into polylactic acid biodegradable microcapsules. With an average particle size of about 95 μm, microcapsules with a desired loading of from 3.65 to 13.80 per cent were prepared. These microcapsules, which contained both crystalline and finely dispersed drug particles, showed a dose-dependent drug release pattern with microcapsules of higher drug loading having a faster release rate than those of lower drug loading. Effective sterilization of the microcapsules for parenteral use was achieved by ⁶⁰Co γ-ray irradiation, which did not affect the microcapsule structure, release rate or drug stability. Mitomycin C showed dose-dependent antiproliferative activity against the growth of the K562 human erythroleukaemia cells. The microencapsulated dosage form of mitomycin C was found to enhance the drug's activity through sustained drug release. In experiments where drug concentrations in the cell medium were reduced according to the drug's biological half-life, the microcapsule systems showed a distinct advantage over the non-capsulated dose for the kinetic inhibition of K562 cell growth.     

Ibuprofen-loaded ethylcellulose/polystyrene microspheres: An approach to get prolonged drug release with reduced burst effect and low ethylcellulose content

The aim of this study was to develop ethylcellulose microspheres for prolonged drug delivery with reduced burst effect. Ethylcellulose microspheres loaded with ibuprofen were prepared with and without polystyrene, which was used to retard drug release from ethylcellulose microspheres. Ibuprofen-loaded ethylcellulose microspheres with a polystyrene content of 0–25% were prepared by the solvent evaporation technique and characterized by drug loading, infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy. The in vitro release studies were performed to study the influence of polystyrene on ibuprofen release from ethylcellulose microspheres. The microspheres showed 28–46% of drug loading and 80–92% of entrapment, depending on polymer/drug ratio. The infrared spectrum and thermogram showed stable character of ibuprofen in the microspheres and revealed an absence of drug polymer interaction. The prepared microspheres were spherical in shape and had a size range of 0.1–4μm. Ethylcellulose/polystyrene micro-spheres showed prolonged drug release and less burst effect when compared to microspheres prepared with ethylcellulose alone. Microspheres prepared with an ethylcellulose/polystyrene ratio of 80:20 gave a required release pattern for oral drug delivery. The presence of polystyrene above this ratio gave release over 24 h. To find out the mechanism of drug release from ethylcellulose/polystyrene microspheres, the data obtained from in vitro release were fitted in various kinetic models. High correlation was obtained in Higuchi and Korsmeyer-Peppas models. The drug release from ethylcellulose/polystyrene microspheres was found to be diffusion controlled.     

Ibuprofen-loaded ethylcellulose/polystyrene microspheres: an approach to get prolonged drug release with reduced burst effect and low ethylcellulose content

The aim of this study was to develop ethylcellulose microspheres for prolonged drug delivery with reduced burst effect. Ethylcellulose microspheres loaded with ibuprofen were prepared with and without polystyrene, which was used to retard drug release from ethylcellulose microspheres. Ibuprofen-loaded ethylcellulose microspheres with a polystyrene content of 0-25% were prepared by the solvent evaporation technique and characterized by drug loading, infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy. The in vitro release studies were performed to study the influence of polystyrene on ibuprofen release from ethylcellulose microspheres. The microspheres showed 28-46% of drug loading and 80-92% of entrapment, depending on polymer/drug ratio. The infrared spectrum and thermogram showed stable character of ibuprofen in the microspheres and revealed an absence of drug polymer interaction. The prepared microspheres were spherical in shape and had a size range of 0.1-4 microm. Ethylcellulose/polystyrene microspheres showed prolonged drug release and less burst effect when compared to microspheres prepared with ethylcellulose alone. Microspheres prepared with an ethylcellulose/polystyrene ratio of 80:20 gave a required release pattern for oral drug delivery. The presence of polystyrene above this ratio gave release over 24 h. To find out the mechanism of drug release from ethylcellulose/polystyrene microspheres, the data obtained from in vitro release were fitted in various kinetic models. High correlation was obtained in Higuchi and Korsmeyer-Peppas models. The drug release from ethylcellulose/polystyrene microspheres was found to be diffusion controlled.     

Microencapsulation using poly(DL-lactic acid) I: Effect of preparative variables on the microcapsule characteristics and release kinetics

Abstract

Poly(DL-lactic acid) (DL-PLA, molecular weight 20 500) microcapsules containing phenobarbitone (PB) as a reference core were prepared using a water/oil (W/O) emulsion system. Surface morphology, particle size and ‘encapsulation efficiency’ of the microcapsules prepared using different preparative variables have been investigated. Buffer pH 9 was used as a dissolution medium to determine the affect of preparative variables on the release rate from these microcapsules.

With an increase in temperature of evaporation the microcapsule surface became increasingly irregular and porous, due to deposition of phenobarbitone crystals near the vicinity of the microcapsule surface leading to rapid release of the core. The normalized release rate was found to increase exponentially with an increase in the temperature of evaporation. Microcapsule morphology was also severely affected due to differences in polymer concentration in the disperse phase solvent. With the increase in polymer concentration, the microcapsule surface was found to be increasingly irregular and non-continuous, due to rapid precipitation of the polymer. Increased polymer concentrations also increased mean microcapsule diameter. The release rate increased with the increase in polymer concentration due to surface defects and did not exhibit a straight line correlation. When core loading was very high (e.g. C:P, 2:1 and 1:1), crystals of phenobarbitone appeared at the surface and these caused a very rapid burst effect. However, microcapsules containing a lower phenobarbitone content were found to follow t^1/2 dependent release. The encapsulation efficiency was not seriously affected due to variations in temperature of preparation and polymer concentration. However, with the decrease in initial core loading the encapsulation efficiency of microcapsules was found to be reduced.     

Preparation of microspheres of water-soluble pharmaceuticals

Abstract

An emulsion-solvent evaporation procedure involving the dispersion of an alcoholic solution of an active in liquid paraffin was used to prepare microspheres of water-soluble pharmaceuticals using ethylcellulose as a carrier. The effects of surfactant, plasticizer, drug loading, and agitation speed on drug release rate from the microspheres were evaluated. The release rates of water-soluble drugs from microspheres, ranging from 100 and 500 μm in diameter, were sustained over an extended time and were found to be related to the ratio of drug to polymer in the final product.     

海藻酸钠-壳聚糖微囊成型机理及其对大分子药物的载药、释药研究海藻酸钠-壳聚糖微囊成型机理及其对大分子药物的载药、释药研究

目的考察海藻酸钠-壳聚糖微囊成型机理及其对大分子药物的载药及释药特性。方法采用乳化胶凝法制备海藻酸钠-壳聚糖微囊,通过差示扫描量热法(DSC)探讨其成型机理。以牛血清白蛋白(BSA)为模型药,研究微囊对大分子药物的包载能力及释药特性。结果DSC分析结果显示,组成微囊的各材料间发生静电相互作用而成型。随药载比增加,微囊中BSA的载药量由9.20％增至35.08％;随壳聚糖浓度升高,载药量由30.29％升至38.12％。载药微囊中BSA在PBS(pH 7.4)与0.1 mol·L^-1 HCl中均呈两相释放;随CTS浓度增大,BSA在0.1 mol·L^-1 HCl中的释放减慢。结论制备的微囊圆整且分散性好,微囊对BSA具较高包载能力,并具一定的缓释作用。