Box-Behnken响应面法优化吲哚美辛口服自微乳剂的处方

Optimization of self-microemulsifying drug delivery system of Indomethacin by Box-Behnken response surface method

目的采用Box-Behnken响应面分析法优化吲哚美辛口服自微乳剂的处方。方法考察吲哚美辛在各种油相、乳化剂、助乳化剂中的溶解度,根据结果绘制伪三元相图,寻找自微乳区域;以油相、乳化剂、助乳化剂为自变量,透光率为因变量,通过对自变量中各种溶媒筛选的多元线性回归及多项式拟合,采用Box-Behnken响应面法优化处方,并进行预测分析。结果处方中吲哚美辛、桉叶油、吐温20、二乙二醇单乙醚占自微乳处方的含量分别为3.1%、15.6%、56.3%、25%;透光率为98.8%±0.17%,平均粒径为14.57±0.77 nm;处方的实际值与预测值偏差为0.20%。结论应用Box-Behnken响应面法能快速、方便地得到吲哚美辛自微乳剂的处方,所建模型预测性良好。

OBJECTIVE To optimize the formula of self- microemulsifying drug delivery system（ SMEDDS） of Indomethacin by Box- Behnken response surface method. METHODS To find the region of indomethacin SMEDDS,pseudo- ternary phase diagram was drawn by the solubility of indomethacin in oil phase,emusifier and co- emusifien. The optimal prescription was determined by using the Box- Behnken design and response surface method. The oil phase,emulsifier and co- emulsifier were independent variables,and light transmittance was the dependent variable. Linear or nonlinear mathematic models were used to estimate the relationship between independent and dependent vailables. Response surfaces were predicted according to the best- fit mathematic models and optimum formulations were selected. RESULTS The optimal prescription of indomethacin SMEDDS composed of indomethacin（ 3. 1%）,Eucalyptus oil（ 15. 6%）,polysorbate- 20（ 56. 3%） and transcutol P（ 25%）. The light transmittance was 98. 8% ± 0. 17% and the mean particle size was 14. 57 ± 0. 77 nm. The deviatio prespription between actual value and the predicted one was 0. 20%. CONCLUSION The optimized formulation of the indomethacin SMEDDS can be obtained quickly and conveniently by the Box- Behnken response surface methodology.