吲哚美辛结肠靶向胶囊的制备及体外释药评价

目的 开发一种结肠靶向胶囊,使吲哚美辛达到结肠部位实现靶向释放。方法 以蘸胶工艺制备不溶性半透膜囊体,灌装药物后以果胶片封住囊体,外套上普通胶囊壳后外包肠溶衣,进行体外释放试验。结果 该给药系统在人工胃液中不变形,药物不释放,采用PEG-2 000∶CA为60%的不溶性囊体,包衣增重90%,药物∶NaCl为1∶1制备的胶囊,药物在人工肠液中3 h释放<10%,在人工结肠液中10 h药物释放超过70%,基本释放完全,达到结肠定位释放要求。结论 吲哚美辛结肠靶向胶囊能实现在结肠定位释放药物。     

肠康宁结肠靶向胶囊体外释放度的评价

目的 对pH依赖型肠康宁结肠靶向胶囊体外释放性能进行评价,探讨制备中药结肠靶向制剂的可行性.方法 以木犀草素为评价指标,采用体外释放度测定法对该制剂的体外释放性能进行评价.结果 体外释放度试验结果表明,木犀草素在人工胃液2h后未见释放,在人工小肠液4h后未见释放,在人工结肠液1h后有一定的释放,2h后释放较高.结论 该制剂能在结肠定位释药.     

酶控渗透泵型结肠定位微丸的制备及体外释放度考察

目的制备以果胶钙和醋酸纤维素为包衣材料,5-氨基水杨酸（5-ASA）为模型药物的酶触发渗透泵型结肠定位微丸,并考察其体外释药特征及释药机制。方法采用包衣锅法制备含药丸芯,选用L9（3）4正交实验设计,以体外释放度为评价指标优化包衣液处方及丸芯中渗透剂的用量,并进行体外释药模型拟合。结果制备5-ASA渗透泵酶触发微丸最佳工艺参数为：包衣增重25%;药物与NaCl（丸芯）比为3∶1;醋酸纤维素与果胶钙（包衣液）用量比为2∶3。所得微丸在人工胃液中2 h,人工小肠液中4 h累计释放率〈8%,人工结肠液12 h累计释放率〉70%,表明结肠定位性较为突出,且可以在结肠持续释放药物以维持局部药物浓度,进一步研究释药机理表明为零级释放。结论采用果胶钙与醋酸纤维素为包衣材料制备渗透泵酶触发结肠定位微丸可实现结肠定位作用。     

结肠定位壳聚糖包衣氟尿嘧啶脂质体的制备、形态与体外释放

目的探讨药物结肠定位壳聚糖包衣脂质体的制备、形态及其在体外释药特性。方法用罗丹明B异硫氰酸(RBITC)和Bodipy-PC分别标记壳聚糖和磷脂,用前体脂质体方法制备氟尿嘧啶脂质体,利用激光扫描共聚焦显微镜观察壳聚糖包衣脂质体的形态;考察壳聚糖包衣脂质体在人工胃液、人工肠液和人工结肠液中的释放。结果 脂质体包衣前后粒径分别为2.071和2.750 μm。壳聚糖能较好地包覆脂质体;3种脂质材料不同的包封率分别为99%,61%,72%。未包衣的脂质体在人工胃液中4 h已释放完全,而包衣脂质体在人工胃液4 h释放6.3%,在人工肠液中8 h仅释放6.8%,但在人工结肠液中释药明显加快,t1/2为3.63 h。结论结肠定位壳聚糖包衣脂质体制备可行,在人工结肠液中,体外释放符合Higuchi方程。     

兰索拉唑肠溶微丸胶囊的制备

目的:制备兰索拉唑肠溶微丸胶囊。方法:采用流化床包衣技术,在空白丸芯上依次包以主药层、隔离层和肠溶层,制备成兰索拉唑肠溶微丸,将肠溶微丸装入普通胶囊制成兰索拉唑肠溶微丸胶囊,并考察3批制剂的载药率及在人工肠液和人工胃液中的释放情况。结果:所制微丸圆整度高,外观亮泽,载药均匀、载药率高(平均值在96%以上),包衣效果好;其在人工肠液中45min的体外累积释放率大于(94.3±0.76)%,在人工胃液中2h的释放量小于(6.2±1.6)%。结论:所制兰索拉唑肠溶微丸胶囊工艺可行,重现性良好,质量稳定可靠,具有良好的体外释药性和耐酸力。     

甲硝唑结肠定位肠溶片的制备及质量控制

目的:研制甲硝唑结肠定位肠溶片的制备工艺和处方,考察其体外释放度并制定该剂型的质量评价标准.方法:模拟服药后该剂型在胃肠道中的生理释药过程,用3种不同pH值的磷酸盐缓冲液作为释放介质,分别在其最大吸收波长277,321和317nm处检测甲硝唑的吸收度,并根据特定时间的药物吸收计算出累计释放度.结果:药片在人工胃液、pH 6.8人工肠液不释药;在pH 7.8人工结肠液中2～20μg穖L-1范围内线性良好,平均回收率104.8%,RSD为0.98%.结论:甲硝唑结肠定位肠溶片的体外释放度检测结果合格.     

肠溶性瑞巴派特壳聚糖胶囊的制备及大鼠口服给药吸收评价

目的评价肠溶性瑞巴派特壳聚糖胶囊的释药作用,考察其结肠定位效果。方法将瑞巴派特1 mg装入壳聚糖胶囊中,并用羟丙基甲基纤维素邻苯二甲酸酯(HPMCP)包裹胶囊,观察胶囊的体外释药性能。在乙醚麻醉下通过聚乙烯管大鼠口服给予瑞巴派特壳聚糖胶囊4 mg,对照组口服同剂量的明胶胶囊和羧甲基纤维素溶液。于给定的时间间隔取血,取出结肠组织,分离提取药物,用HPLC法测定大鼠血液及结肠中药物浓度。结果在6 h体外溶出试验中,即人工胃液2 h和人工肠液4 h中,瑞巴派特从壳聚糖胶囊中的释药量的质量分数小于10%。大鼠口服瑞巴派特壳聚糖胶囊时,在结肠黏膜中的药物含量-时间曲线下面积(AUCLI0-9,16.01 mg.h.L-1)分别是明胶胶囊和羧甲基纤维素溶液的2.5倍和4.4倍。口服瑞巴派特壳聚糖胶囊,大鼠血浆药物含量-时间曲线下面积(AUCPL0-9)为1.02 mg.h.L-1,同剂量的明胶胶囊和羧甲基纤维素溶液分别是2.16 mg.h.L-1和1.89 mg.h.L-1,表明在壳聚糖的作用下,与明胶胶囊或羧甲基纤维素溶液比较,瑞巴派特从胃肠道吸收进入血液循环的量较少。结论在HPMCP的保护下,壳聚糖是瑞巴派特在结肠释药的一种有效的载体。     

美沙拉嗪结肠靶向微丸的制备和体外评价

目的以结肠溶型丙烯酸树脂为包衣材料制备美沙拉嗪pH控制型结肠靶向微丸,评价其体外释药特性。方法挤出滚圆法制备美沙拉嗪微丸,采用L934正交设计实验优化工艺条件,流化床包衣机包衣,采用U884均匀设计试验优化工艺参数,考察了微丸圆整度、收率及体外释药特性。结果优化条件所得的微丸外观圆整,粒径分布均匀,收率高,在人工胃液中2h、人工小肠液中4h累计释放率<5%,人工结肠液1h累计释放率>95%,具有明显的结肠靶向释药特性。结论美沙拉嗪结肠靶向微丸具有良好的体外结肠靶向释药特性,可进一步进行体内释药行为考察。     

左氧氟沙星羧甲基壳聚糖微球结肠靶向释药的实验研究

目的:检测所制备的左氧氟沙星羧甲基壳聚糖(LVFX/CMC)微球在人工消化液中和大鼠体内结肠靶向释药的性能。方法:以分光光度仪测定微球在人工消化液中的累积释放量,电镜观察微球在人工消化液中形态的改变。SD大鼠60只,随机分为两组,分别以LVFX/CMC微球(含40 mg左氧氟沙星)及等量左氧氟沙星溶剂灌胃,以高效液相色谱法对LVFX/CMC微球和左氧氟沙星(LVFX)灌胃后大鼠盲肠、结肠中药物浓度进行定量检测。结果:左氧氟沙星壳聚糖微球在人工胃液介质中溶解缓慢,2 h仅释药8.62%;在人工小肠液介质中溶解速度稍见加快,6 h释药29.39%,但表现为药物缓释曲线,24 h仅释药42.13%;在人工结肠液中,4 h后释药84.56%,24 h内累积释药量为93%。扫描电镜观察人工胃液中的微球明显溶胀,稍见变形;人工结肠液中的微球溶解,粒径明显减小。灌胃后LVFX/CMC微球组5和9 h时段盲肠、结肠药量明显高于LVFX组。结论:左氧氟沙星羧甲基壳聚糖微球在体外、体内实验中的释放符合结肠靶向释药的特点。     

重组人粒细胞集落刺激因子壳聚糖胶囊的制备和体外释药特性

目的 :制备人重组粒细胞集落刺激因子 (rhG CSF)冻干粉剂壳聚糖胶囊 ,并对其体外释药性能进行评价。方法 :将rhG CSF冻干粉剂装入壳聚糖胶囊中 ,再以邻苯二甲酸羟丙基甲基纤维素 (HPMCP)包裹胶囊 ,用氮兰四唑蓝 (MTT)比色法测定其在人工胃液及小肠液中的体外释放性能。将荧光素钠 (FS)作为模型化合物在相同条件下进行实验 ,以激发波长 470nm、发射波长 5 13nm荧光检测FS壳聚糖胶囊在人工大肠液中的体外释放性能。用扫描电镜法评价壳聚糖胶囊在大肠内容物中的降解作用。结果 :在人工大肠液中壳聚糖具有明显降解作用。rhG CSF壳聚糖胶囊在人工胃液 (2h)和人工小肠液 (6h)内累积释药量为 (15 .5± 6 .5 ) % ,n =6。而在人工大肠液中 ,FS壳聚糖胶囊 4h释药基本完全。结论 :用HPMCP包膜的rhG CSF壳聚糖胶囊具有潜在的结肠靶向释药特性。     

4-氨基水杨酸钠结肠定位片的研究

目的制备一种新型口服结肠定位制剂，并考察其体外释药行为与犬体内的结肠定位特性。方法本试验选择4-氨基水杨酸钠作为模型药物，应用丙烯酸树脂Eudragit RL30D，RS30D和Eudragit FS30D分别作为缓释和肠溶层包衣材料，制得包衣片剂，使系统可依赖pH和时间双重机制释药。在体外释放试验中，系统在0.1 mol·L^-1盐酸溶液中运转2 h后，分别在pH为6.5，7.0或7.4的磷酸盐缓冲液中继续运转12 h。体内验证以放射性同位素锝（^99mTc）做标记，用γ-射线显影法来确定系统在胃肠道内的释药时间和位置。结果体外实验中，系统在0.1 mol·L^-1盐酸溶液中运转2 h后无药物释放，在pH高于6.5的介质中缓慢释药，介质的pH越高，药物释放越快。体内实验中， 包衣片在胃肠道上半部无药物释放， 到达结肠后开始释药； 而非包衣片在犬胃部即迅速崩解。结论本文采用的包衣材料使包衣片到达升结肠时开始释放药物，药物释放时间可达10 h以上。     

氟比洛芬肠溶片的制备及其体外释放度研究

目的:制备氟比洛芬肠溶片并考察其体外释放特性。方法:以乙基纤维素(EC)、甲基丙烯酸共聚物(Eudragit S100)、乳糖为辅料,采用直接压片法制备制剂;考察处方中不同辅料用量对药物释放的影响及其在0.1mol·L-1盐酸溶液(HCl)和pH6.8磷酸盐缓冲液(PBS)中的体外释放特性。结果:以EC0.250g、Eudragit S1000.750g、乳糖3.750g时组成的处方可在HCl中不释放,在PBS中完全释放达94.20%。结论:该制剂处方设计和制备方法可行,其释放行为符合设计要求。     

5-氨基水杨酸pH依赖-菌群触发型结肠定位给药系统的体外释放性能

目的研究5-氨基水杨酸（5-ASA）pH依赖-菌群触发型结肠定位给药系统的体外释放性能。方法将5-ASA装于以瓜尔豆胶和Eudragit S 100包膜的胶囊中,采用Diamonsil TM-C₁₈（250mm×4.6mm,5μm）色谱柱,柱温25℃,流速1.0mL·min^-1,检测波长为240nm,测定其在pH 1.2 HCl、pH6.8和7.4 PBS溶液中的体外释放性能。结果 5-ASA胶囊的3批样品在pH 1.2 HCl、pH 6.8 PBS溶液中几乎不释药,在pH 7.4 PBS溶液中有释药。增重34%样品在pH 7.2 PBS和pH 7.2 PBS+β-甘露聚糖酶的溶液中,释放无明显差异;而增重44%样品有差异。结论用瓜尔豆胶和Eudragit S 100包膜的5-ASA胶囊具有良好的结肠定位释药效果。     

Production of enteric capsules by means of hot-melt extrusion.

The aim of this study was to develop an alternative technique for enteric coating consisting of the hot-melt extrusion of coating polymers. An enteric coating polymer (PVAP or HPMC AS), premixed with a plasticizer, was extruded into hollow cylinders. The hollow pipes were filled with a model drug and both open ends of the cylinders were closed, yielding hot-melt extruded enteric capsules. Main advantages of this new technology are the continuity of the process and its application for the formulation of moisture sensitive active ingredients. The enteric capsules showed excellent gastro-resistance, since no drug release was observed after 2 h 0.1N HCl. The influence of wall thickness (0.15, 0.3, 0.5, 0.8, and 1.0 mm) of the capsules on drug release was investigated. Enteric capsules with a wall thickness of 1.0 mm were subjected to a pH gradient dissolution method, simulating passage through the gastro-intestinal tract, in order to evaluate their suitability for ileal or colonic drug targeting. Storing the capsules for 1 month at high relative humidity (RH) (60 and 75% RH) revealed that the HPMC AS capsules were superior to the PVAP capsules. It can be concluded that hot-melt extruded capsules seem suitable as an alternative for enteric coating.     

乳化溶剂扩散法制备罗红霉素肠溶微球及影响因素考察

目的罗红霉素肠溶微球的制备及影响因素考察。方法应用肠溶高分子材料 ,采用乳化溶剂扩散法一步制备罗红霉素肠溶微球。对影响微球形态、粒度分布、收率及其在 0 . 1mol·L-1盐酸溶液和 pH 6 8磷酸盐缓冲溶液中累积释放度的处方因素、制备条件和溶剂系统进行了考察。应用X 射线粉末衍射实验考察了药物在微球中的分散状态。结果制备的微球外观圆整。微球粒径随着搅拌转速的增加而减小。微球收率随架桥剂用量减少 ,良溶剂用量增加而增加 ;并且受到不良溶剂中乳化剂种类的影响。药物在 0 . 1mol·L-1盐酸溶液中的释放速率随肠溶材料HP- 5 5用量增加显著降低。当HP- 5 5与药物质量比大于 5时 ,药物在 0 . 1mol·L-1盐酸溶液中释放小于 5 % (w) ,同时在pH 6 . 8磷酸盐缓冲溶液中可迅速释放。X- 射线粉末衍射结果显示 ,微球中药物已被高度分散 ,形成固体分散体。结论乳化溶剂扩散法适用于制备具有固体分散体结构的肠溶微球。     

吲哚美辛酶解型结肠靶向片的初步研究

采用湿法制粒压片制备吲哚美辛瓜尔胶骨架片,并测定了模拟人体胃肠道生理环境下的体外释放度.结果表明,骨架片5h内释药不超过20%;26h内不加酶组的总释药量不超过40%,加酶组为88%左右,能达到结肠靶向给药的效果.     

In-vitro evaluation of khaya and albizia gums as compression coatings for drug targeting to the colon

Khaya and albizia gums were evaluated as compression coatings for target drug delivery to the colon using indometacin (a water insoluble drug) and paracetamol (a water soluble drug) as model drugs. The core tablets were compression-coated with 300 and 400 mg of 100% khaya gum, 100% albizia gum and a mixture of khaya and albizia gum (1:1). Drug release studies were carried out in 0.1(M) HCl (pH 1.2) for 2 h, Sorensen's buffer (pH 7.4) for 3 h and then in phosphate-buffered saline (pH 6.8) or in simulated colonic fluid for the rest of the experiment to mimic the physiological conditions from the mouth to colon. The results indicated that khaya and albizia gums were capable of protecting the core tablet in the physiological environment of the stomach and small intestine, with albizia gum showing greater ability than khaya gum. The release from tablets coated with the mixture of khaya and albizia gums was midway between the two individual gums, indicating that there was no interaction between the gums. Studies carried out using rat caecal matter in phosphate-buffered saline at pH 6.8 (simulated colonic fluid) showed that the gums were susceptible to degradation by the colonic bacterial enzymes, leading to release of the drug. The results demonstrate that khaya gum and albizia gum have potential for drug targeting to the colon.     

The formation and permeability of drugs across free pectin and chitosan films prepared by a spraying method.

This study has investigated the permeation of drugs through free films made of pectin and chitosan. The background for this study is the intended use of the films as coating material in a colon-specific drug delivery device. The factors that varied when making the films were the pectin source and grade of the pectin, degree of deacetylation of the chitosan and ratio between pectin and chitosan. The permeability of the model drug in 0.1 M HCl was low with an average drug release of 1.3 x 10(-3)%/cm. The films containing high content of chitosan showed exponential kinetics while the films containing high content of pectin showed 0-order kinetics. The release of drug in phosphate buffer pH 6.8 showed 0-order kinetics. The lowest permeability was obtained for a film consisting of a high content of pectin to chitosan, chitosan with a high degree of deacetylation and non-amidated low methoxylated citrus pectin. The permeation of paracetamol for this combination was 9.4 x 10(3)%/cm. This film combination had a combined diffusion of only 0.046%/cm after 1 h in 0.1 M HCl and 4 h in phosphate buffer pH 6.8.     

Design,optimization and evaluation of mesalamine matrix tablet for colon drug delivery system

The aim of the present investigation was to develop and evaluate matrix tablet of mesalamine for colonic delivery by using Eudragit RSPO, RLPO and combination of both. The tablets were further coated with different concentration of pH-dependent methacrylic acid copolymers (Eudragit S100), by dip immerse method. The physicochemical parameters of all the formulations were found to be in compliance with the pharmacopoeial standards. The in vitro drug release study was conducted using sequential dissolution technique at pH 1.2 (0.1N) HCl, phosphate buffers pH 6.8 and 7.4, with or without rat cecal content mimicking different regions of gastro intestinal tract. The result demonstrated that the tablet containing Eudragit RLPO coated with Eudragit S100 (1 %) showed a release of 94.91 % for 24 h whereas in the presence of rat cecal content the drug release increases to about 98.55 % for 24 h. The uncoated tablets released the drug within 6 h. The in vitro release of selected formulation was compared with marketed formulation (Octasa MR). In vitro dissolution kinetics followed the Higuchi model via non-Fickian diffusion controlled release mechanism. The stability studies of tablets showed less degradation during accelerated and room temperature storage conditions. The enteric coated Eudragit S100 coated matrix of mesalamine showing promising site specific drug delivery in the colon region.     

熔融挤出法制备阿司匹林肠溶颗粒

目的优化熔融挤出法制备阿司匹林肠溶颗粒的配方和方法。方法以pH值1.2介质中耐酸性与pH值6.8介质中的溶出度为评价指标;以星点设计方法优选肠溶材料与辅料配比。结果以79.8%醋酸羟丙甲纤维素琥珀酸酯为肠溶材料,4.2%十八醇为释药调节剂,3.0%微粉硅胶为润滑剂,于130℃下挤出,过程顺利,颗粒均一;所得载药颗粒在pH值1.2盐酸中2 h溶出(9.1±0.56)%,在pH值6.8缓冲液中45 min溶出(72.42±3.06)%。结论熔融挤出法制备阿司匹林肠溶颗粒简便、可靠。