那格列奈/盐酸二甲双胍双层片的处方优化

目的:优选由那格列奈速释层与盐酸二甲双胍缓释层组成的双层片处方。方法:先以盐酸二甲双胍在2、4、8h时点的释放度与理想值的偏差之和(γ)为评价指标制备缓释层(12h),并采用正交试验设计优选处方;然后在缓释层处方一定的条件下制备双层片,以那格列奈在45min的释放度(Q)为评价指标优化速释层的处方。结果:盐酸二甲双胍缓释层的最佳处方为羟丙基甲基纤维素K4M20%,黏合剂为10%聚维酮K30(PVP)乙醇溶液;那格列奈速释层的最佳处方为乳糖40%,低取代羟丙基纤维素30%,黏合剂为10%PVP乙醇溶液。结论:正交试验优化的双层片处方良好,达到了设计要求。

Optimization of the Formula of Nateglinide/Metformin Hydrochloride Double-layer Tablets

OBJECTIVE ： To optimize the formula of the double - layer tablet of nateglinide rapid - release layer and metformin hydroehloride sustained- release layer. METHODS： The total deviation （γ） between release percentage and ideal value of metformin hydroehloride at 2, 4 and 8 hours was used as the evaluation standard to prepare sustained - release layer which can release up to 12 hours, with its formulation optimized by orthogonal experiment design. Under a certain condition of the formulation of the sustained - release layer, the double - layer tablet was prepared with the release percentage（Q） of nateglinide at 45 min as the evaluation standard to optimize the formulation of the rapid - release layer. RESULTS： The optimized formulation of metformin hydrochloride sustained- release layer was 20% K4M plus 10% PVP - ethanol as adhesive. The optimized formulation of nateglinide rapid - release layer was 40% lactose plus 30% low - substituted hydroxypropyl cellulose and ethanol containing 10% PVP- ethanol as adhesive. CONCLUSION： The formulation of the optimized double- layer tablet is satisfactory and up to the standard of the design.