塞来昔布自微乳化释药系统的制备及体内外评价

摘要

目的 将塞来昔布制备成自微乳化释药系统(SMEDDS)以增加药物的溶出速度,并提高药物在大鼠体内的生物利用度.方法 采用伪三元相图法确定了塞来昔布-SMEDDS的最优处方,并评价了其经水稀释后形成的微乳外观、微观形态、粒径分布及体外释放行为;以塞来昔布混悬液为对照,测定塞来昔布-SMEDDS经大鼠口服的生物利用度.结果 塞来昔布-SMEDDS处方组成为:中链三酰甘油(油相),聚山梨酯-20(乳化剂),二乙二醇单乙基醚(助乳化剂),最佳配比为2∶9∶9.塞来昔布-SMEDDS经水稀释后形成的微乳外观呈淡蓝色透明状液体;透射电镜下显示其大小均匀,呈圆整球状分布,平均粒径为(57.6±14.2) nm;SMEDDS显著提高了塞来昔布的体外溶出速度;塞来昔布-SMEDDS和塞来昔布混悬液的药物浓度-时间曲线下面积分别为(5.54±0.94)和(3.32±0.59) mg·L-1·h,相对生物利用度为166.9%.结论 将塞来昔布制备成SMEDDS可显著提高药物的体外溶出速度和体内生物利用度.%Objective To investigate celecoxib self-microemulsifying drug delivery system (CXB-SMEDDS) that was developed to increase the dissolution rate and oral bioavailability of celecoxib.Methods The formulation of CXB-SMEDDS was optimized by pseudo-ternary phase diagrams analysis.The appearance, morphology, particle size distribution and in vitro drug release behavior of CXB-SMEDDS were investigated after diluted by water.The bioavailability of CXB-SMEDDS was determined by oral administration to rats compared with CXB suspension.Results An optimized formulation was selected: Medium chain triglycerides as oil phase, Tween 20 as surfactant, Transcutol HP as cosurfactant.The ratio of oil phase, surfactant and cosurfactant was 2∶9∶9.Upon mixing with water, CXB-SMEDDS formed a clear and transparent microemulsion solution with homogeneous small spherical under transmission electron microscopy.For particle size of CXB-SMEDDS was found to be (57.6±14.2) nm.The in vitro dissolution test indicated a significant improvement in release characteristics of CXB.The AUC of CXB-SMEDDS and CXB suspension were (5.54±0.94) and (3.32±0.59) mg·L-1·h, respectively.The relative bioavailability was 166.9%.Conclusion The SMEDDS can significantly increase celecoxib dissolution in vitro and bioavailability in vivo.