Khan Furquan Nazimuddin, Dehghan Mohamed Hassan G
Y. B. Chavan College of Pharmacy, Department of Pharmaceutics, Dr. Rafiq Zakaria Campus, Rauza Bagh, Aurangabad-431001, India.
Sci Pharm. 2012 Jan-Mar;80(1):215-28. doi: 10.3797/scipharm.1104-26. Epub 2011 Nov 5.
Atorvastatin calcium, a lipid-lowering drug, is much less bioavailable because of reduced solubility in acidic media. Multiple-unit floating microcapsules of Atorvastatin calcium (ATC) were developed to expand the gastric residence time of the drug, as ATC has maximum rate of absorption in the upper GI tract. Floating microcapsules were prepared by Emulsion-solvent evaporation technique through incorporation of dioctyl sodium sulphosuccinate (DSS) as a dissolution enhancer. The microcapsules were assessed for shape, size, drug entrapment efficiency, stability and in-vitro drug dissolution rate and were subjected to SEM, DSC and PXRD studies. The ATC-loaded floating microcapsules were spherical in shape and had the particle size of about 28.10 μm and drug-loading efficiency of about 96.55 %. The floating microspheres containing DSS had significantly higher drug dissolution rates than those without DSS. The best formulation, AT4, consisting of Ethyl cellulose, DSS and Poly Ox®, had a maximum drug dissolution rate of 97.86 %, as compared to Storvas 80 mg (Ranbaxy Ltd, as a reference) which had a rate of only 54% during a period of 12 h in acidic media. A pharmacokinetic study performed on albino rabbits illustrates that the bioavailability of AT4 floating microcapsules significantly increased to nearly 1.7 times that of Storvas 80 mg. The present study indicates that the use of multi-unit floating microcapsules for delivery of ATC can improve its bioavailability.
阿托伐他汀钙是一种降脂药物，由于在酸性介质中的溶解度降低，其生物利用度较低。由于阿托伐他汀钙（ATC）在上消化道的吸收速率最高，因此开发了多单元漂浮微胶囊以延长该药物在胃中的停留时间。通过乳液-溶剂蒸发技术，加入磺基琥珀酸二辛酯钠（DSS）作为溶出促进剂来制备漂浮微胶囊。对微胶囊的形状、大小、药物包封率、稳定性和体外药物溶出速率进行了评估，并进行了扫描电子显微镜（SEM）、差示扫描量热法（DSC）和粉末X射线衍射（PXRD）研究。载有ATC的漂浮微胶囊呈球形，粒径约为28.10μm，载药效率约为96.55%。含有DSS的漂浮微球的药物溶出速率明显高于不含DSS的微球。最佳配方AT4由乙基纤维素、DSS和聚氧化乙烯组成，其最大药物溶出速率为97.86%，而作为对照的80mg舒降之（兰伯西有限公司）在酸性介质中12小时内的溶出速率仅为54%。对白化兔进行的药代动力学研究表明，AT4漂浮微胶囊的生物利用度显著提高，几乎是80mg舒降之的1.7倍。本研究表明，使用多单元漂浮微胶囊递送ATC可提高其生物利用度。
