响应面法制备格列美脲环糊精包合物

目的 制备格列美脲 - 羟丙基 -β- 环糊精包合物并对其处方进行优化。方法 通过 Box-Behnken 响应面法,在单因素实验的基础上以稀释剂比例、黏合剂浓度和崩解剂比例为考察因素,以环糊精包合物片的释放度为评价指标对处方进行优化;用红外光谱法表征制备的包合物,并对制得的格列美脲片进行质量评价,拟合体外释放曲线。结果 响应面法优化得到最佳处方为：稀释剂 - 乳糖和 MCC 的比例为 7.37:1,黏合剂 -PVP 的浓度为 6%,崩解剂 -CMS-NA 的比例为 6.45%;按此条件进行 3组平行实验,所得验证值为 88.13%,回归方程所得理论预测值为 88.69%,两者相对误差为 0.64%。红外光谱显示形成了格列美脲包合物;其溶解度为 68.53μg/mL,较格列美脲原料药提高了 50.39 倍。结论 体外释放实验表明 HP-β-CD 格列美脲片相比普通格列美脲片的释放度有显著提高,响应面法优化格列美脲包合物处方可行,为格列美脲片进一步开发奠定了良好的理论基础。

Preparation of glimepiride cyclodextrin inclusion complexusing response surface methodology

Objective To prepare the inclusion complex of glimepiride with hydroxypropyl-β-cyclodextrin(HP-β-CD) and to optimize its formulation. Methods The prescription was optimized by the Box-Behnken responsesurface methodology (RSM) with the diluent ratio, adhesive concentration, and disintegrant ratio as the investigationfactors and the release rate of tablets as the evaluation index based on the single factor experiment. The preparedinclusion complex was characterized by infrared spectroscopy, and the quality of the tablets was evaluated and thein vitro release curve was fitted. Results The optimal formulation was as followed: the ratio of diluent-lactose toMCC was 7.37:1, the concentration of binder-PVP was 6%, and the ratio of disintegrant-CMS-NA was 6.45%. Theconditions were carried out in three sets of parallel experiments, and the obtained verification value was 88.13%.The theoretical prediction value of the regression equation was 88.69% and the relative error was 0.64%. Infraredspectroscopy showed the formation of glimepiride clathrate; its solubility was 68.53μg/mL, which was 50.39 timeshigher than that of glimepiride. Conclusions The in vitro release test showed that the release rate of HP-β-CDglimepiride tablets was significantly higher than that of common glimepiride tablets. It is feasible to optimize theprescription of glimepiride inclusion complex using RSM, which offers a good theoretical support for the furtherdevelopment of glimepiride