磺胺嘧啶微囊体外释药行为及影响因素考察

考察了用喷雾干燥法制备的磺胺嘧啶微囊的体外溶出过程。药物初期呈零级释放，后期释放呈指数关系。药物释放有明显的滞流层现象。释药初期累积溶出量对时间变化的斜率（ｋ）与搅拌速率的平方根的倒数呈直线关系。药物释放速率随微囊粒径减少而增加。囊材分子量和阻滞剂用量增加，使药物释放速率降低。附加剂滑石粉对药物释放的影响较复杂，随着滑石粉比例增加，药物释放速率增加，但至一定比例后，速率降低。     

正交法研究盐酸克林霉素-乙基纤维素微囊的处方工艺

目的 制备盐酸克林霉素微囊,选择最优处方工艺。方法 以乙基纤维素为囊材,采用液中干燥法制备盐酸克林霉素微囊。采用四因素三水平正交实验设计考察药物与囊材的比例、油水相比例、表面活性剂用量、抗粘剂用量对微囊粒径、载药量和包封率的影响。结果 确定处方药物与囊材的比例为3：2,油水相比例为3：1,司盘用量为0．5％．滑石粉与囊材的质量比为1：1为最佳处方工艺。结论 本法处方合理,制备工艺可行,有良好的应用前景。     

喷雾干燥法制备吡哌酸缓释微囊

用喷雾干燥法制备吡哌酸缓释微囊,以乙基纤维素作囊材,硬脂酸作阻滞剂,制备的微囊能明显延缓药物的释放。药物释放速率随其含量增加而增加,释药的表观扩散系数随微囊粒径降低而降低。家兔体内药物动力学研究结果表明,与片剂相比,吡哌酸微囊口服后,血药浓度维持时间较长。     

对乙酰氨基酚/阿拉伯胶-壳聚糖多层微囊的制备及其体外释药研究

目的:制备对乙酰氨基酚多层微囊并考察其体外释药性能和机制。方法:以阿拉伯胶和壳聚糖为囊材,以戊二醛为交联剂,使用溶液干燥法(复合乳液法)制备载药(对乙酰氨基酚)多层(阿拉伯胶-壳聚糖-阿拉伯胶-壳聚糖)微囊。通过正交试验,以阿拉伯胶溶液-二氯甲烷体积比(A)、壳聚糖用量(B)、戊二醛-成壳材料总量比例(C)为因素,包封率为指标,优选制备工艺。通过测定其在盐酸溶液中的体外累积释药率并进行释放动力学模型拟合分析其释药机制。结果:最佳工艺条件为A4:3、B0.6g、C1:3。所制备的多层微囊球形完整、光滑,囊壁较厚;突释效果不明显,药物在12h内全部释放,其体外释药机制符合Ritger-Peppas模型。结论:所制载药多层微囊突释效应小、缓释效果较好。     

液中干燥法制备盐酸小檗碱药物树脂缓释微囊的研究

目的研究液中干燥法制备盐酸小檗碱药物树脂缓释微囊的处方工艺。方法以司盘-85-液体石蜡-丙酮为乳化体系,丙烯酸树脂RL100为囊材,邻苯二甲酸二乙酯为增塑剂,采用正交设计法优化处方。结果盐酸小檗碱药物树脂缓释微囊的最佳处方为：包衣液浓度为15％,增塑剂浓度为15％,药物树脂与囊材比为4：1。结论该法制备的盐酸小檗碱药物树脂缓释微囊具有良好缓释效果,12h累计释放量〉90％。     

单硝酸异山梨酯微囊的制备及其释药特性

以乙基纤维互为囊材，采用液中干燥法制备单硝酸异山梨酯微囊，通过药物的体外释放确定处方，评价微囊的缓释效果。结果表明，所得单硝酸异山梨酯乙基纤维素微囊收率高，粒径大小、粒径分布及含药量均符合设计要求。     

利用喷雾干燥法制备肠溶微囊的研究

目的采用喷雾干燥法制备肠溶微囊，建立微囊质量评价方法。方法采用丙烯酸树脂Ⅱ号为包衣材料，蓖麻油为增塑剂，乙醇为溶剂，阿司匹林为囊心物，将囊材与囊心物按1：2和1：4的比例喷雾干燥制成微囊。结果经扫描电镜和差示量热扫描法测定表明，微囊包囊形成，囊心物、囊材按1：4较好，微囊能迅速在人工肠液中释放，45分钟释药达75％，而肠溶片45分钟释药低于60％。结论喷雾干燥法制备肠溶微囊方法简单，工艺稳定，改变丙烯酸树脂Ⅱ号比例可控制药物释放速率。     

盐酸维拉帕米不溶性微孔膜缓释胶囊的制备和体外释药试验

目的制备盐酸维拉帕米不溶性微孔膜胶囊剂并研究其体外释药行为。方法以乙酸纤维素（CA）为囊膜材料,聚乙二醇400为增塑剂,蘸胶法制备囊壳,并从致孔剂种类、比例、不同释放条件和内容物配方等因素考察盐酸维拉帕米的释药行为,通过扫描电镜对释药后囊壳结构进行观察。结果选用泊洛沙姆为致孔剂,增加其用量能使药物释放加快;囊内添加柠檬酸,能使药物释放更平稳。结论维拉帕米不溶性微孔膜缓释胶囊在体外能得到缓释效果,通过胶囊内微环境的控制,可以得到平稳的体外释药速度。     

可分剂量甲磺酸二氢麦角碱缓释微囊片的制备及体外释放机制的研究

目的对可分剂量甲磺酸二氢麦角碱缓释微囊片(EDDTEM)的处方进行研究,并研究其体外释放机制。方法以海藻酸钠-壳聚糖为囊材,采用复凝聚法制备甲磺酸二氢麦角碱缓释微囊(EEM)并压制成片,采用正交设计实验优化处方。结果EEM的最优处方为:海藻酸钠与药物比例为6∶1,海藻酸钠-壳聚糖比例为4∶1,海藻酸钠浓度为2.5%。所制缓释片释药行为符合Higuchi方程,释药机理为扩散和溶蚀并存。结论EDDTEM具有良好的体外缓释效果,可进一步进行体内释药行为考察。     

可分剂量甲磺酸二氢麦角碱缓释微囊片的制备及体外释放机制的研究

目的 对可分剂量甲磺酸二氢麦角碱缓释微囊片(EDDTEM)的处方进行研究,并研究其体外释放机制。方法 以海藻酸钠-壳聚糖为囊材,采用复凝聚法制备甲磺酸二氢麦角碱缓释微囊(EEM)并压制成片,采用正交设计实验优化处方。结果 EEM的最优处方为：海藻酸钠与药物比例为6∶1,海藻酸钠-壳聚糖比例为4∶1,海藻酸钠浓度为2.5%。所制缓释片释药行为符合Higuchi方程,释药机理为扩散和溶蚀并存。结论 EDDTEM具有良好的体外缓释效果,可进一步进行体内释药行为考察。     

Ranitidine Hydrochloride-loaded Ethyl Cellulose and Eudragit RS 100 Buoyant Microspheres: Effect of pH Modifiers

A floating type of dosage form of ranitidine hydrochloride in the form of microspheres capable of floating on simulated gastric fluid was prepared by solvent evaporation technique. Microspheres prepared with ethyl cellulose, Eudragit^® RS100 alone or in combination were evaluated for percent yield, drug entrapment, percent buoyancy and drug release and the results demonstrated satisfactory performance. Microspheres exhibited ranitidine hydrochloride release influenced by changing ranitidine hydrochloride-polymer and ranitidine hydrochloride-polymer-polymer ratio. Incorporation of a pH modifier has been the usual strategy employed to enhance the dissolution rate of weakly basic drug from floating microspheres. Further citric acid, fumaric acid, tartaric acid were employed as pH modifiers. Microspheres prepared with ethyl cellulose, Eudragit^® RS100 and their combination that showed highest release were utilized to study the effect of pH modifiers on ranitidine hydrochloride release from microspheres which is mainly affected due to modulation of microenvironmental pH. In vitro release of ranitidine hydrochloride from microspheres into simulated gastric fluid at 37° showed no significant burst effect. However the amount of release increased with time and significantly enhanced by pH modifiers. 15% w/w concentration of fumaric acid provide significant drug release from ranitidine hydrochloride microspheres prepared with ranitidine hydrochloride:ethyl cellulose (1:3), ranitidine hydrochloride:Eudragit^® RS100 (1:2) and ranitidine hydrochloride:ethyl cellulose:Eudragit^® RS100 (1:2:1) whereas citric acid, tartaric acid showed significant cumulative release at 20% w/w. In all this study suggest that ethyl celluose, Eudragit^® RS100 alone or in combination with added pH modifiers can be useful in floating microspheres which can be proved beneficial to enhance the bioavailability of ranitidine hydrochloride.     

油中干燥法制备甘氨酸茶碱钠微囊及其释药特性的研究

采用油中干燥法，以ＥｕｄｒａｇｉｔＲＳ１００和Ｅｕｄｒａｇｉｔ ＲＬ１００为囊材制备水溶性药物甘氨酸茶碱钠微囊。实验结果表明，所得微囊能延缓药物的释放，且以ＥｕｄｒａｇｉｔＲＳ１００为囊材制得到的微囊缓释性能较优。     

乙基纤维素膜中壬苯醇醚的释放

目的考察水不溶高分子乙基纤维素薄膜中具有两亲性质的壬苯醇醚的释放行为,考察水微溶阳离子表面活性剂三甲基十六烷基溴化铵的添加对壬苯醇醚释放的影响。方法以刮板法制备5种乙基纤维素载药薄膜,使壬苯醇醚载药量与乙基纤维素质量比为1.5∶10.0、5.0∶10.0、10.0∶10.0、20.0∶10.0、40.0∶10.0,同样以刮板法制备6种添加有三甲基十六烷基溴化铵的薄膜,使壬苯醇醚,三甲基十六烷基溴化铵与乙基纤维素质量比1.5∶0.5∶10.0、1.5∶1.0∶10.0、5.0∶0.5∶10.0、5.0∶1.0∶10.0、10.0∶0.5∶10.0、10.0∶1.0∶10.0。以去离子水为释放介质,37℃,120 r.min-1条件下考察药物的释放,采用HPLC法测定释放介质中药物的量,绘制8 h内的药物累计释放曲线并进行拟合。结果乙基纤维素薄膜中壬苯醇醚载药量的高低,可以使得其8 h内的释放行为从没有释放到30 min内完全突释,2个系列的样品具有缓释能力,并且载药量越大同一时间点乙基纤维素薄膜中壬苯醇醚的释放量越大。添加三甲基十六烷基溴化铵能促进壬苯醇醚的释放。具有缓释行为的样品的释药曲线对Higuchi's和1级释放方程拟合均较好。结论在乙基纤维素薄膜中,壬苯醇醚的载药量可以影响其自身的释放行为,三甲基十六烷基溴化铵的添加和增多可加速壬苯醇醚的释放,为研究其它类型乙基纤维素/壬苯醇醚共混系统药物释放行为提供了参考。     

Microencapsulation of propranolol hydrochloride by the solvent evaporation technique.

Propranolol hydrochloride microcapsules were prepared by the coacervation-phase separation induced by solvent evaporation technique. The cellulose acetate phthalate was employed as coating material alone and in combination with ethyl cellulose. The prepared microcapsules were evaluated for their drug content, particle size distribution (microscopic method), flow properties, bulk density, in vitro dissolution and drug release kinetics.     

Floating microspheres of cimetidine: formulation, characterization and in vitro evaluation

The present study involves preparation and evaluation of floating microspheres with cimetidine as model drug for prolongation of gastric residence time. The microspheres were prepared by the solvent evaporation method using polymers hydroxypropylmethyl cellulose and ethyl cellulose. The shape and surface morphology of prepared microspheres were characterized by optical and scanning electron microscopy, respectively. In vitro drug release studies were performed and drug release kinetics was evaluated using the linear regression method. Effects of the stirring rate during preparation, polymer concentration, solvent composition and dissolution medium on the size of microspheres and drug release were also observed. The prepared microspheres exhibited prolonged drug release (approximately 8 h) and remained buoyant for > 10 h. The mean particle size increased and the drug release rate decreased at higher polymer concentration. No significant effect of the stirring rate during preparation on drug release was observed. In vitro studies demonstrated diffusion-controlled drug release from the microspheres.     

In vitro and in vivo evaluation of ranitidine hydrochloride loaded hollow microspheres in rabbits

The objective of this investigation was to develop the hollow microspheres as a new dosage form of floating drug delivery systems with prolonged stomach retention time. Hollow microspheres containing ranitidine hydrochloride (RH) were prepared by a novel solvent diffusion-evaporation method using ethyl cellulose (EC) dissolved in a mixture of ethanol and ether (6:1.0, v/v). The yield and drug loading amount of hollow microspheres were 83.21±0.28% and 20.71±0.32%, respectively. The in vitro release profiles showed that the drug release rate decreased with increasing viscosity of EC and the diameter of hollow microspheres, while increased with the increase of RH/EC weight ratio. Hollow microspheres could prolong drug release time (approximately 24 h) and float over the simulate gastric fluid for more than 24 h. Pharmacokinetic analysis showed that the bioavailability from RH-hollow microspheres alone was about 3.0-times that of common RH gelatin capsules, and it was about 2.8-times that of the solid microspheres. These results demonstrated that RH hollow microspheres were capable of sustained delivery of the drug for longer period with increased bioavailability.     

红景天苷缓释微胶囊的制备及体外释放特性研究

目的:制备红景天苷微胶囊,测定其包封率,并考察其体外释药特性。方法:以生物相容性良好的壳聚糖和海藻酸钠为囊壁材料,红景天苷药物微粒为囊芯,采用静电吸引层层纳米自组装技术(LBL法)制备红景天苷微胶囊。结果:制备的微胶囊包封率较高,达到78.02±0.72%;不同包裹层数的微胶囊在体外释放速度不同。结论:用LBL法制备的红景天苷微胶囊具有较高的包封率和缓释特性,具有一定的应用前景。     

Asymmetric membrane capsules of phenylephrine hydrochloride: an osmotically controlled drug delivery system

The aim of the current study was to develop osmotically controlled release system of freely water soluble drug phenylephrine hydrochloride by use of asymmetric membrane capsules to reduce the dosing frequency and consequently improve the patient compliance. Ethyl cellulose asymmetric membrane capsules were developed by phase inversion process and solubility modulation was accomplished by common ion effect wherein sodium chloride was included in the formulation that also served as an osmogen. The effect of formulation variables namely level of polymer (ethyl cellulose), level of pore former (glycerol) and level of osmogen (sodium chloride) on the in vitro release of the drug was evaluated by 2(3) factorial design. Effects of environmental factors on the release rate of the drug from asymmetric membrane capsules were also evaluated. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and inner porous region for the prepared asymmetric membrane. The dimensional analysis of asymmetric membrane capsule documented the capsules to be of uniform cap and body size comparable to commercial hard gelatin capsules. In vitro release studies results showed that incorporation of higher amount of osmogen not only increased the osmotic pressure but also controlled the drug release for a period of 12 hr. The drug release was inversely proportional to the level of polymer in asymmetric membrane capsule but directly related to the level of pore former in the membrane. The optimized asymmetric membrane capsule (F5) was able to provide zero order release of phenylephrine hydrochloride independent of agitation rate, intentional defect in the membrane and pH of dissolution medium but was dependent on the osmotic pressure gradient between inside and outside of the delivery system.     

The prolongation of the in vitro dissolution of a soluble drug (phenethicillin potassium) by microencapsulation with ethyl cellulose

Microcapsules of phenethicillin potassium as a model water-soluble drug, coated with ethyl cellulose, have been prepared (core: wall ratios 1:1, 1:2 and 1:3) in which the taste has been masked, the odour almost eliminated and the release retarded. Sieve analysis showed that with decreasing core: wall ratios there was a trend towards increasing amounts of larger sized microcapsules. At constant core: wall ratios in vitro release of drug was generally greatest from the larger microcapsules. This result correlated with the surface areas of the microcapsules which became less as the asymmetry of the microcapsules diminished with decrease in microcapsule size. There was a linear relation between the amount of ethyl cellulose and the time for 60% release of drug, and the release pattern was analogous to that from insoluble porous matrices. Scanning electron micrographs showed the microcapsules to be irregularly shaped with circular surface pores, and they did not alter in shape or size during dissolution. Tableting of 1:1 core: wall ratio microcapsules significantly further retarded the dissolution.