多单元双嘧达莫胃漂浮缓释制剂的制备及其处方优化

Preparation and optimization of multiple-unit gastric-floating sustained-release dosage form of dipyridamole

目的制备多单元胃漂浮制剂双嘧达莫胃漂浮缓释微丸,并考察其体外漂浮和释放性质。方法采用挤出滚圆法制备轻质含药丸芯,底喷流化床包衣技术将乙基纤维素(EC)喷于含药丸芯表面形成缓释膜材,控制微丸的漂浮性和药物的释放特性;采用正交试验设计对包衣微丸的处方进行优化和筛选,并对最佳处方进行验证试验及释放模型拟合。结果包衣液中致孔剂含量质量分数为20%、增塑剂含量质量分数为5%、包衣质量分数增加为4%时,所得微丸的体外漂浮性和缓释释放度均达到了要求。12 h微丸的漂浮率大于90%,8 h累计释放量达到85%以上,包衣微丸的释药符合一级释药模型。结论自制产品质量稳定,工艺简单可靠,所得的胃漂浮缓释微丸达到了缓释与漂浮的双重要求。

Objective To study the preparation of multiple-unit formulation-DIP gastric-floating sustained-release micro-pills and its evaluation in vitro. Methods The extrusion-rolling method was taken to prepare light-weight pill cores and bottom-spraying technology of fluid bed was performed to spray EC on the surface of pill cores to form sustained-release membrane to control the floatability of micro-pills and its drug release. Orthogonal designed test was used to optimize and select formulation of coated micro-pellets, then the reproducibility of the optimal formulation was tested and the release model was fitted. Results When coated micro-pills were prepared under the optimal prescription, its floating ability and release characters both reached the requirements：drug release rate was over 85% after 8 h, micro-pills floating percent was over 90% after 12 h and its release properties fit to first-order model. Conclusions The preparation method of the micro-pills is feasible and reliable. The products reach the requirements of floatability and sustained-release at the same time.