硝苯地平脉冲片的研制及其体外释药特性

Preparation of Nifidipine Pulsatile Release Tablets

目的 制备硝苯地平脉冲片 ,考察处方及释放条件对体外释药行为的影响 ,解析其释放机理。方法 混合粉末直接压片 ,滚转包衣锅法分别双层包衣 (溶胀层和释放衣层 )。通过测定释放度研究脉冲片的制剂学特征。结果 双层包衣片以脉冲形式释放 ,释药时滞随释放衣层厚度增加而延长 ,释药速率减小 ;渗透压活性物质和溶胀层可提高快速释放期的释药速率。释放介质 p H值和搅拌速度对释药行为无影响。释药机理包括扩散、溶胀和渗透泵机理。结论 调整释放衣膜厚度和组成可获得理想的脉冲释药行为。本给药系统设计可推广应用于水不溶性药物的脉冲给药系统研究。

Objective To prepare nifidipine (NFP) bi-layered pulsatile release tablets, to evaluate the effects of the formulation and dissolution medium on drug release behavior, and to elucidate the mechanism of drug release based on the obtained results. Methods Core tablets containing osmotic active agent were prepared by direct compression and spray coated with swelling layer and semipermeable membrane subsequently. Pharmaceutical properties of NFP pulsatile tablets were investigated by dissolution test. Results Pulsatile release of NFP from bi-layered tablets was accomplished. The lag-time was prolonged with the increase of coating level of semipermeable membrane, and the steady release rate was increased significantly with the increase of osmotic active agent and swelling layer. It was shown that drug release behaviors were constant and irrespective of various pH values of dissolution medium and rotation speeds. All results indicated that diffusion, swelling and osmotic pumping were involved in the mechanism of drug release. Conclusion Ideal pulsed release behaviors can be achieved by adjusting the coating level and composition of semipermeable membrane to meet the requirement of chronotherapy. The comprehensive mechanism of drug release is suitable for water insoluble drugs.