Study on Formulation Optimization and Drug-release Mechanism of Cilnidipine Sustained-release Tablet / 中国药房

ABSTRACT

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 11(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.