左卡尼汀胃漂浮缓释片的制备及体外评价

Develepment and In Vitro Evaluation of Floating Matrix Tablets of Levocarnitine

目的:应用Box-behnken效应面法优化左卡尼汀胃漂浮缓释片处方,并评价其体外漂浮和释放特性。方法:以粉末直接压片法制备片剂。采用单因素法筛选出主要影响因素,即硬度、HPMC用量及碳酸氢钠用量,以漂浮性能和不同时间点释药性能为评价指标,通过Box-behnken设计实验优化处方,对体外释药数据进行方程拟合,并结合扫描电子显微镜对溶出前后片剂表面形态的观察,探讨其释药机理。结果:优选处方为每片含HPMCK100M 29.7%,碳酸氢钠5.0%,十八烷醇15.0%,硬度为4 kg.mm-2。体外释药符合Makoid-Banakar模型,药物的释药机制为骨架溶蚀与药物扩散双重作用。结论:Box-behnken效应面法可用于左卡尼汀胃漂浮缓释片处方优化,且制备工艺简单,优化处方具漂浮缓释作用。

Objective：To develop an optimized gastric floating drug delivery system containing levocarnitine as a model drug by Box-behnken design/response surface methodology and to evaluate the in vitro characteristic of the formulation.Methods：Tablets were prepared by a direct powder compression method.The independent variables were screened out through an one-way method as the hardness of tablets and the amounts of HPMCK 100M and Sodium bicarbonate.Floating lag time（FLT）,total floating time（TFT） and the releases of drug in 1 h,4 h and 8 h were selected as dependent variables.The possibly optimal formulation was predicted by the response surface method.The drug release mechanism of the tablet was studied by model-fitting of drug released with different equations and imaging of tablet surfaces by scanning electron microscopy before and after dissolution.Results：Optimized formulation of levocarnitine gastric floating tablets was propose to consist of 29.7% HPMCK 100M,5% sodium bicarbonate and 15% octacosanol,with the hardness of tablets at 4 kg·mm-2;the Makoid-Banakar mechanism was found to be predominant,which indicated that water diffusion as well as polymer rearrangement played an essential role in the drug release.Conclusion：The quadratic mathematical model developed could be used to predict formulations with desired release and floating properties.