王学霞，刘庆娜，庞淑慧

（山东大学第二医院门诊药房，济南 250033）

西尼地平缓释片的处方优化及释药机制研究

王学霞＊，刘庆娜，庞淑慧

（山东大学第二医院门诊药房，济南 250033）

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。

西尼地平；缓释片；Box-Behnken响应面法；释药机制

ABSTRACTOBJECTIVE：To optimize the formulation of Cilnidipine sustained-release tablet，and study its drug-release mechanism.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 degree 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-release tablet，and verification test was conducted.The drug-release mechanism of Cilnidipine sustained-release tablet was investigated 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：Cilnidipine sustained-release tablet with sustained-release effect is successfully prepared by optimized formulation.

KEYWORDSCilnidipine；Sustained-release tablet；Box-Behnken response surface method；Drug-release mechanism

钙通道阻滞药是一类应用广泛的降压药物。西尼地平作为新一代的二氢吡啶类钙通道阻滞药，能同时阻滞L型和N型通道，是强效双通道阻滞药[1]。西尼地平于1995年首先在日本上市，国内现有剂型主要为普通片剂和胶囊剂。但由于西尼地平水溶性差、生物利用度低，严重影响了其临床应用。为了提高西尼地平的水溶性、延长其作用时间，本研究先将西尼地平制成了固体分散体，再将其制备成了西尼地平缓释片，并采用Box-Behnken响应面法优化了其处方，研究了其释药机制。……