西尼地平缓释片的处方优化及释药机制研究

摘要

OBJECTIVE:To optimize the formulation of Cilnidipine sustained-release tablet,and study its drug-release mecha-nism. METHODS:Solvent method was adopted to prepare the cilnidipine solid dispersion,then Cilnidipine sustained-release tablet was prepared by using hypromellose K4M(HPMC K4M)as release material. Using comprehensive scores of cumulative release de-gree in 2,6,12 h as indexes,single factor method and Box-Behnken response surface method were used to screen the amounts of HPMC K4M and ethyl cellulose (EC),lactose-microcrystalline cellulose (MCC) ratio in formulation of Cilnidipine sustained-re-lease tablet,and verification test was conducted. The drug-release mechanism of Cilnidipine sustained-release tablet was investigat-ed by model fitting way. RESULTS:The optimal formulation was as follow as 25％ of cilnidipine solid dispersion,30％ of HPMC K4M,10％ of EC,lactose-MCC ratio of 1:1(m/m). The adhesive was 5％ PVPP ethanol solution and the lubricant was 0.5％magnesium stearate. The cumulative release degrees of prepared sustained-release tablet in 2,6,12 h were(21.4±3.3)％,(62.9± 2.8)％,(85.4±0.5)％(n=3),relative error of which to predicted value 25％,60％,90％were 14.4％,4.8％and 5.1％. Release curve showed the highest fitting degree with the first-order release model,conforming to non-Fick diffusion. CONCLUSIONS:Cil-nidipine sustained-release tablet with sustained-release effect is successfully prepared by optimized formulation.%目的:优化西尼地平缓释片处方,研究其释药机制.方法:采用溶剂法制备西尼地平固体分散体,再以羟丙甲纤维素K4M(HPMC K4M)为缓释材料制备西尼地平缓释片.利用单因素法和Box-Behnken响应面法,以2、6、12 h累积释放度的综合评分为指标,筛选西尼地平缓释片处方中HPMC K4M用量、乙基纤维素(EC)用量、乳糖-微晶纤维素(MCC)比例,并进行验证.通过模型拟合的方式考察西尼地平缓释片的释药机制.结果:最优处方为西尼地平固体分散体25％、HPMC K4M 30％、EC 10％、乳糖-MCC(1:1,m/m),黏合剂为5％的聚乙烯吡咯烷酮乙醇溶液,润滑剂为0.5％的硬脂酸镁.所制缓释片2、6、12 h时的累积释放度分别为(21.4±3.3)％、(62.9±2.8)％、(85.4±0.5)％(n=3),与预期值25％、60％、90％的相对误差分别为14.4％、4.8％、5.1％;释放曲线与一级释药模型拟合度最高,符合non-Fick扩散机制.结论:按优化后的处方成功制得具有缓释作用的西尼地平缓释片.