Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.
AAPS PharmSciTech. 2010 Mar;11(1):294-303. doi: 10.1208/s12249-010-9380-5. Epub 2010 Feb 25.
An oral sustained release dosage form of cinnarizine HCl (CNZ) based on gastric floating matrix tablets was studied. The release of CNZ from different floating matrix formulations containing four viscosity grades of hydroxypropyl methylcellulose, sodium alginate or polyethylene oxide, and gas-forming agent (sodium bicarbonate or calcium carbonate) was studied in simulated gastric fluid (pH 1.2). CNZ release data from the matrix tablets were analyzed kinetically using Higuchi, Peppas, Weibull, and Vergnaud models. From water uptake, matrix erosion studies, and drug release data, the overall release mechanism can be explained as a result of rapid hydration of polymer on the surface of the floating tablet and formation of a gel layer surrounding the matrix that controls water penetration into its center. On the basis of in vitro release data, batch HP1 (CNZ, HPMC-K100LV, SBC, LTS, and MgS) was subjected to bioavailability studies in rabbits and was compared with CNZ suspension. It was concluded that the greater bioavailability of HP1 was due to its longer retention in the gastric environment of the test animal. Batch no. HP1 of floating tablet in rabbits demonstrated that the floating tablet CNZ could be a 24-h sustained release formulation.
研究了一种基于胃漂浮基质片的盐酸桂利嗪(CNZ)口服缓释剂型。在模拟胃液(pH 1.2)中,研究了含有四种粘度级别的羟丙基甲基纤维素、海藻酸钠或聚乙烯氧化物以及产气剂(碳酸氢钠或碳酸钙)的不同漂浮基质配方中 CNZ 的释放情况。使用 Higuchi、Peppas、Weibull 和 Vergnaud 模型对基质片中的 CNZ 释放数据进行了动力学分析。从水合作用、基质侵蚀研究和药物释放数据来看,整体释放机制可以解释为漂浮片表面聚合物的快速水合作用以及在基质周围形成控制水渗透到其中心的凝胶层的结果。基于体外释放数据,对批 HP1(CNZ、HPMC-K100LV、SBC、LTS 和 MgS)进行了兔体内生物利用度研究,并与 CNZ 混悬剂进行了比较。结果表明,HP1 的生物利用度更高是由于其在试验动物的胃环境中滞留时间更长。兔用漂浮片批 HP1 表明,漂浮片 CNZ 可以是一种 24 小时持续释放制剂。
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