蛇床子素固体分散体分散片的处方优化及其体内外质量评价

目的:优化蛇床子素固体分散片的处方并考察其体内外释药特性。方法:以崩解时限、硬度的综合评分为指标,通过正交试验优选蛇床子素固体分散片的处方。采用RP-HPLC比较蛇床子素固体分散片和原料药体内外释药特性的差异。结果:最佳处方为蛇床子素固体分散体43.5%,微晶纤维素40%,交联聚维酮12%,低取代羟丙基纤维素4%,微粉硅胶0.5%;崩解时间(80.5±3.8)s,硬度(4.4±0.4)kg,分散均匀性好、混悬性好。分散片体外释药参数T50(药物溶出50%时间)和Td(药物溶出63.2%时间)分别为0.013,1.37 min,均明显优于原料药。固体分散片的达峰时间(tmax)1.00 h,达峰浓度(Cmax)37.42 mg·L-1,药时曲线下面积(AUC0~t)43.04 mg·L-1·h。结论:蛇床子素固体分散片具有分散均匀、有效成分溶出速率快的特性,能显著提高药物在大鼠体内的生物利用度。

Formulation Optimization and Quality Evaluation of Osthole Solid Dispersion Dispersible Tablets

Objective: To optimize the formulation of osthole solid dispersible tablets and investigate its in vitro release characteristics. Method: Taking composite score of disintegration and hardness as index,formulation of osthole solid dispersible tablets was optimized by orthogonal test.Release characteristics of osthole solid dispersible tablets and osthole were investigated by RP-HPLC. Result: The proportion of each adjuvant in optimal formulation was 40% of microcrystalline cellulose (MCC),4% of low-substituted hydroxypropyl cellulose (L-HPC),12% of crosslinked polyvidone (PVPP),43.5% of osthole solid dispersion and 0.5% of aerosil.The tablets disintegrated in 80.5 s,the hardness was 4.4 kg,the dispersible uniform was excellent.Release parameters of osthole solid dispersible tablets were remarkly better than these of osthole group;t_max of osthole solid dispersible tablets group was1 h,its C_max was 37.42 mg·L^-1,AUC_0-t was 43.04 mg·L^-1·h. Conclusion: Osthole solid dispersible tablets has characteristics of uniformly dispersing and quick releasing of active constituents,it can significantly inprove the bioavailability of osthole in rats.