Box-Behnken设计-响应面法优化明胶胶皮处方

Optimization of Gelatin Film Shell Formulation by Box-Behnken Design-response Surface Methodology

采用加热明胶、部分脱水山梨醇、甘油和水的混合物来制备明胶胶液,并加入遮光剂等其他成分制备明胶胶皮。以明胶种类、部分脱水山梨醇与甘油质量比、二氧化钛比例为自变量,以物质迁移率、平衡溶胀量、水蒸气透过率、透光率和崩解时间为因变量,采用Box-Behnken设计-响应面法优化胶皮处方,所得优化处方为:采用冻力150 g骨明胶,部分脱水山梨醇与甘油的质量比为2.3∶10,二氧化钛占明胶比例为1.18%。采用优化处方制备了3批胶皮,质量评价结果显示,其物质迁移率、平衡溶胀量、透光率的预测值与实测值偏差均≤1.7%,批间RSD均≤0.36%,表明所建立的优化处方准确性高、重现性好、稳定性良好。该研究为软胶囊工业化生产的改进提供了方法学参考。

A gel solution was prepared by heating the mixture of gelatin,partially dehydrated sorbitol,glycerin and water.An opacifier and other ingredients were added into above solution to obtain the gelatin film shell.A BoxBehnken design-response surface method was employed to optimize the gelatin film shell with material mobility,equilibrium swelling amount,water vapor permeability,light transmittance,and disintegration time as the dependent variables,and with gelatin grade,the mass ratio of partially dehydrated sorbitol to glycerin,and the proportion of titanium dioxide as the independent variables.The optimal gelatin film shell formulation was as follows:the gelatin strength was 150 g bloom,the mass ratio of partially dehydrated sorbitol to glycerin was 2.3∶10,and the proportion of titanium dioxide to gelatin was 1.18%.Three consecutive batches of gelatin film shell were manufactured based on the optimized formulation.The deviations of actual material mobility values,equilibrium swelling amount,and light transmittance from the predicted values were no more than 1.7%.The inter-batch RSD did not exceed 0.36%.These results indicated that the optimized gelatin film shell formulation had good accurate,reproducible and stability.This study could provide some references to improve the industrialized production of soft capsules.