复方阿托伐他汀钙与依折麦布胶囊剂的处方优化研究

Study on prescription optimization of the compound atorvastatin calcium and ezetimibe capsule

目的:星点设计-效应面优化法设计复方阿托伐他汀钙依折麦布胶囊的最佳处方及工艺。方法:对复方制剂采取分开制粒的方式,首先利用单因素考察方法大致确定处方中部分辅料的种类与用量,然后分别采用正交设计和星点设计,主要以药物在PBS 4.5和水两种介质中的溶出度为评价指标,进行筛选优化,以期得到最佳的处方与工艺。结果:经处方筛选确定最终处方为:依折麦布部分:依折麦布10 mg;十二烷基硫酸钠(SDS)10 mg;聚维酮(PVP)40 mg;微晶纤维素(MCC)70 mg;羧甲基淀粉钠(CMSNa)50 mg。阿托伐他汀钙部分:阿托伐他汀钙10 mg;Na HCO310 mg;羟丙基纤维素(HPC)50 mg;MCC 28.2 mg;一水乳糖80 mg。硬脂酸镁外加1.8 mg。结论:按照最终确定的复方阿托伐他汀钙依折麦布胶囊的处方与工艺所制得制剂性状良好,含量均匀,与对照制剂相比,溶出行为相似。

Objective： To optimize the prescription and technology of atorvastatin calcium and ezetimibe of capsule compound by central composite design and response surface. Methods： The two medicines were granulated individually. Single factor method was applied to determine types and approximate amounts of some materials used in the prescription at first, then orthogonal experimental design and central composite design-response surface methodology were used to screen and optimize the prescription and the preparation process by the evaluation criteria of dissolutions in medium of sodium acetate 4.5 and aqueous. Results： The ultimate prescription was determined as follows. The part of Ezetimibe consisted of ezetimibe 10 mg; SDS 10 mg; PVP 40 mg; MCC 70 mg;CMS-Na 50 mg. The part of atorvastatin calcium is composed by atorvastatin calcium 10 mg; NaHCO3 10 mg; HPC 50 mg; MCC 28.2 mg and lactose monohydrate 80 mg. Besides, 1.8 mg magnesium stearate was mixed out of above two parts. Conclusion： Preparations with the optimized prescription of the compound capsules of ezetimibe and atorvastatin calcium show good traits and uniform content. Compared with the control formulation, its dissolution behavior is similar.