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盐酸维拉帕米的口服缓释生物黏附片剂制剂

Per-oral extended-release bioadhesive tablet formulation of verapamil HCl.

作者信息

Elkheshen Seham, Yassin Alaa Eldeen B, Alkhaled Fayza

机构信息

College of Pharmacy, Cairo University, Cairo, Egypt.

出版信息

Boll Chim Farm. 2003 Jun;142(5):226-31.

PMID:14526657
Abstract

The objective of this study was to formulate a hydrogel-forming bioadhesive drug delivery system for oral administration of verapamil HCl (VP). This system is a non-distintegrating gastro-retentive tablet to allow continuous slow release of VP in the stomach medium where it is more soluble. Different formulate of VP tablets were prepared by compression using various proportions of hydroxypropyl cellulose (HPC) and carbopol 934p (CP). The effect of polymer concentration on the release profile, water uptake and in vitro bioadhesion was studied. Five formulae (F3-F7) exhibited slow release profiles. Formulations F6 (40% HPC and 30% CP) and F7 (40% HPC and 40% CP) had the slowest. They showed 63.6 and 52.2% drug release, respectively, after 12 hours. The kinetic analysis of the release data demonstrated that the bigbest linearity were achieved when data fitted in Higuchi equation rather than zero or first order equations. They had n values close to 0.5 that confirming their Higuchi diffusion. F3 showed the highest swelling index (101.2%), however, the detachment force was intermediate (1.427 N/cm2). Formulae (F4-F7) showed relatively strong in-vitro bioadhesive force. They had detachment forces higher than 1 N/cm2. In general, a delay in drug release and an increase in the in-vitro bioadhesion was seen with the increase in both polymer concentrations. The in vitro data revealed that Formulae F4-F7 served the dual purpose of bioadhesion and sustained release.

摘要

本研究的目的是制备一种用于口服盐酸维拉帕米(VP)的水凝胶形成型生物粘附药物递送系统。该系统是一种不崩解的胃滞留片,可使VP在其溶解度更高的胃介质中持续缓慢释放。通过使用不同比例的羟丙基纤维素(HPC)和卡波姆934p(CP)进行压片制备了不同配方的VP片。研究了聚合物浓度对释放曲线、吸水率和体外生物粘附性的影响。五个配方(F3-F7)呈现出缓释曲线。配方F6(40% HPC和30% CP)和F7(40% HPC和40% CP)的释放最慢。12小时后,它们的药物释放率分别为63.6%和52.2%。释放数据的动力学分析表明,当数据符合Higuchi方程而非零级或一级方程时,线性度最佳。它们的n值接近0.5,证实了其Higuchi扩散。F3显示出最高的溶胀指数(101.2%),然而,其分离力处于中等水平(1.427 N/cm2)。配方(F4-F7)显示出相对较强的体外生物粘附力。它们的分离力高于1 N/cm2。总体而言,随着聚合物浓度的增加,药物释放延迟,体外生物粘附性增加。体外数据表明,配方F4-F7兼具生物粘附和缓释的双重作用。

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