硝苯吡啶水凝胶型骨架片剂的研制

STUDIES ON HYDROPHILIC GEL MATRIX TABLET OF NIFEDIPINE

根据水凝胶骨架释放机制,研制了硝苯吡啶溶蚀型骨架片剂A。其体外溶出行为符合一级动力学过程。体外环境如介质、桨速不影响其溶出行为。片剂A的体内血浓用气相色谱法测定,其体内配置状态以二室模型描述较为适宜,经计算机模型嵌合程序迭代处理求得动力学参数。生物等效性研究表明:片A与国外长效片B无显著差异,而与市售普通片C有显著差异。A相对于B和C的生物利用度分别为97.66%和281.80%。稳定性试验表明片剂A对光不稳定,温度、湿度对其基本无影响。薄膜包衣延缓了药物的光解。

A nifedipine matrix tablet (A) was prepared by using hydrophilic polymer. The dissolution behaviors of nifedipine formulation were tested by the paddle method. It was found that the dissolution behavior of A was little affected by in vitro environment, i. e., pH, stirring speed. A specific gas chromotography with electron capture detection for nifedipine was developed, In vivo profiles of its preparations were demonstrated to fit two-compartment model. The pharmacokinetic parameters were calculated by using non-linear regression computer program. The bio-equivalence study showed that no statistical differences occurred in AUC, C_(max), T_(max)etween A and one sustained-release tablet from aboard (B), but differences occurred between A and one conventional tablet (C). The extent of bioavailability was 97.66% of B and 281.80% of C. An accelerated testing method was used to investigate the effect of temperature, humidity and light on the stability of A. It was confirmed that nifedipine is a photoinstable compound. Light-protective effect of coating-film is very marked. A TLC method was used to detect photodegradation product.