目的 优化内异消复方缓释滴丸各组分同步释药的处方，探讨其释药机制。方法 以药载比（X₁）、乙基纤维素质量分数（X₂）、PEG 6000质量分数（X₃）和硬脂酸质量分数（X₄）为考察因素，以“释放区间”值为指标，采用Doehlert设计-响应曲面优化法对内异消复方缓释滴丸的处方进行优化。用DDsolver软件拟合体外释药规律。结果 优化处方：X₁为1∶12，X₂为12%，X₃为30%，X₄为20%。模拟的胃肠道环境下，阿魏酸与川芎嗪、阿魏酸与延胡索乙素和川芎嗪与延胡索乙素的相似因子（f₂^*）值分别为53.37、56.17、57.85。阿魏酸的释放符合一级动力学方程和Higuchi方程，川芎嗪和延胡索乙素符合Baker-Lonsdale方程和Ritger-Peppas方程。结论 优化的内异消复方缓释滴丸能实现各组分的同步缓慢释放，其释放机制以扩散为主。

Objective To optimize the formulation of Neiyixiao Compound Sustained-release Dropping Pills which could release active compositions at synchronic rate and to investigate its releasing mechanism. Methods The Doehlert design and response surface method were used to optimize the formulation. Four independent variables, the ratio of drug and matrix (X₁), the content of ethylcellulose (X₂), PEG 6000 (X₃), and stearic acid in matrix (X₄) were investigated. The “interval of released amount” was established as response. DDsolver software was used to fit releasing models. Results The optimal formulation was as following: the ratio of drug and matrix was 1∶12, the content of ethylcellulose, PEG 6000, and stearic acid in matrix were 12%, 30%, and 20%, respectively. Under the simulated gastrointestinal pH conditions, the values of similarity factor (f₂^*) of ferulic acid and ligustrazine, ferulic acid and tetrahydropalmatine, and ligustrazine and tetrahydropalmatine were 53.37, 56.17, and 57.85, respectively. The release profile of ferulic acid complied with first-order kinetics and Higuchi equations, and those of ligustrazine and tetrahydropalmatine were in accordance with Baker-Lonsdale and Ritger-Peppas equations. Conclusion The optimal formulation of compound sustained-release dropping pills makes it possible that each component could get to sustained-release synchronously. The release mechanism is diffusion.

科技部“重大新药创制”科技重大专项（010ZX09401-306-3-16）；“国家大学生创新性实验计划”项目（101063515）