阿昔莫司缓释片的体外释放度及释放机制的初步研究

Dissolution behavior and mechanism in vitro of acipimox sustained-release tablets

目的:研制凝胶骨架型阿昔莫司缓释片,考察其体外释放度,并对药物的释放机制进行初步研究。方法:以羟丙基甲基纤维素(HPMC)为骨架材料,将阿昔莫司制成凝胶骨架型缓释片,考察HPMC种类及用量、填充剂种类及用量和制备工艺等因素对阿昔莫司缓释片体外释放速率的影响。结果:HPMC的种类、用量和片剂表面积对阿昔莫司体外释放速率有明显的影响;填充剂的种类及制备工艺对释放速率基本无影响;篮法、桨法及转速对释放速率基本无影响。阿昔莫司缓释片的释放机制为非纯Fickian扩散(non-Fickian)机制,即为药物扩散和骨架溶蚀协同作用的结果,其中扩散机制起主要支配作用。结论:用高黏度HPMC作为亲水凝胶骨架片基质能达到较好的缓释作用。

Objective: To determine the dissolution behavior and mechanism of acipimox sustained-released matrix tablets. Methods: Acipimox sustained-release matrix tablets were prepared by mixing of acipimox with the matrix hydroxypropyl methylcellulose (HMPC) that was used as hydrophilic polymer and additives followed by compression of the HMPC and additives into acipimox tablets. The factors affecting the acipimox release rate in vitro from the matrix, including types and quantity of HPMC and additives, and manufacturing procedures were evaluated. Results: The types and quantity of HPMC used in matrixes and the tablet surface area were closely associated with the acipimox release. The types and quantity of additives and manufacturing procedures, e. g. dissolution apparatus and rotating speed,showed no significant effects on the acipimox release. The slow release of acipimox from the matrix resulted from the synergism of the acipimox diffusion and matrix degradation, which obeys non-Fickian diffusion mechanism. The diffusion factor plays a main role in the entire dissolution. Conclusion: The employment of the matrix HPMC provided sustained release better in the matrix tablets.