甘草总黄酮微海绵的制备及体外释放度评价

目的:优选甘草总黄酮微海绵的制备工艺并考察其体外释放度。方法:利用类乳剂溶媒扩散法制备甘草总黄酮微海绵,以微海绵得率、包封率及分散系数为指标,通过星点设计-效应面法考察聚乙烯醇用量、药物与乙基纤维素的比例、搅拌速度对甘草总黄酮微海绵制备工艺的影响。利用紫外分光光度法测定甘草总黄酮微海绵的包封率,检测波长335 nm;建立HPLC同时测定甘草总黄酮中甘草苷、异甘草苷、甘草素、异甘草素、甘草查尔酮A和光甘草定的含量,检测波长300 nm,流动相乙腈-甲醇-0.2%磷酸水溶液梯度洗脱;利用透析法比较甘草总黄酮及甘草总黄酮微海绵中6个成分的体外释放度。结果:甘草总黄酮微海绵的最佳制备工艺为聚乙烯醇用量2.69%,药物-乙基纤维素(6∶1),搅拌速度1 100 r·min~(-1),搅拌时间4 h。8 h内甘草总黄酮中甘草苷、异甘草苷、甘草素、异甘草素、甘草查尔酮A和光甘草定的累积释放度分别为87.47%,86.83%,76.98%,78.48%,86.58%和56.58%,24 h内甘草总黄酮微海绵中这6个成分的累积释放度分别为91.45%,89.74%,77.57%,82.64%,87.74%和67.74%。结论:利用类乳剂溶媒扩散法制备的甘草总黄酮微海绵粒径大小均匀、工艺稳定且操作简便。甘草总黄酮微海绵具有明显的缓释作用。

Preparation and in Vitro Release of Glycyrrhizae Radix et Rhizoma Flavonoids Microsponges

Objective: To optimize preparation technology of Glycyrrhizae Radix et Rhizoma flavonoids microsponges and investigate its in vitro release. Method: Glycyrrhizae Radix et Rhizoma flavonoids microsponges were prepared by quasi-emulsion solvent diffusion method,taking yield of microsponges,encapsulation efficiency and dispersion coefficient as indexes,central composite design-response surface methodology was adopted to investigate effect of dosage of polyvinyl alcohol(PVA),ratio of drug and ethyl-cellulose,stirring speed on preparation procedure of the microsponges.Encapsulation efficiency of the microsponges was determined by UV spectrophotometry.The content of six major ingredients in Glycyrrhizae Radix et Rhizoma flavonoids were investigated simultaneously by HPLC,detection wavelength was 300 nm,mobile phase was acetonitrile-methanol-0.2% phosphoric acid aqueous solution for gradient elution.Difference of in vitro release between Glycyrrhizae Radix et Rhizoma flavonoids and the microsponges was compared by dialysis method. Result: Optimum preparation technology of the microsponges were as follows: PVA amount of 2.69%,drug-ethyl-cellulose(6:1),stirring speed of 1 100 r·min^-1,stirring time of 4 h.Within 8 h,cumulative release rates of liquiritin,isoliquiritin,liquiritigenin,isoliquiritigenin,licochalcone A and glabridin in Glycyrrhizae Radix et Rhizoma flavonoids were 87.47%,86.83%,76.98%,78.48%,86.58% and 56.58%;within 24 h,cumulative release rates of these components were 91.45%,89.74%,77.57%,82.64%,87.74% and 67.74%,respectively. Conclusion: Glycyrrhizae Radix et Rhizoma flavonoids microsponges are homogeneous with an obvious sustained release property,and the optimum preparation technology is stable and simple.