美洛昔康自微乳化释药系统的处方设计、优化及质量评价

Formulation design, optimization and quality evaluation of meloxicam self-microemulsifying drug delivery systems

【目的】制备美洛昔康自微乳化释药系统(Mel-SMEDDSs),并评价其质量。【方法】根据溶解度实验和伪三元相图确定Mel-SMEDDSs处方中油相、表面活性剂和助表面活性剂的种类及用量范围,最终选择油相浓度(X1)、表面活性剂浓度(X2)和助表面活性剂浓度(X3)3个因素,以粒径分布(Y1),多聚分散系数(PDI,Y2)和10 min药物溶出度(Y3)作为评价指标,采用"三因素三水平Box-Behnken实验设计"优化Mel-SMEDDSs处方。Mel-SMEDDSs加水分散形成淡蓝色微乳,通过透射电镜观察其形态,马尔文激光粒度仪测定其粒径分布、PDI以及Zeta电位;比较美洛昔康原料药与Mel-SMEDDSs的体外药物溶出情况;考察Mel-SMEDDSs的稳定性。【结果】优化得到Mel-SMEDDSs的最佳处方组成为:单油酸甘油酯用量为30 g,辛酸癸酸聚乙二醇甘油酯用量为74 g,二乙二醇单乙基醚用量为17.5 g,加水分散后形成类球状微乳,大小分布均匀,平均粒径为(181.7±7.9)nm,PDI为(0.251±0.006),Zeta电位为(-10.4±1.4)mV。与美洛昔康原料药相比,Mel-SMEDDSs可显著提高药物的溶出速度,在10 min药物溶出度达到(92.4±1.9)%。Mel-SMEDDSs加速条件下放置45 d稳定性良好。【结论】本研究将美洛昔康制备成自微乳化释药系统,可以显著提高药物的溶出速度,有望提高美洛昔康的口服生物利用度,值得进一步研究。

【Objective】To prepare meloxicam self-microemulsifying drug delivery systems(Mel-SMEDDSs)and evaluate its quality.【Methods】According to the solubility experiment and pseudo-ternary phase diagram,the types and suitable combination of oil phase,surfactant and co-surfactant were determined."Box-Behnken design(3-factor,3-level)"was utilized for the optimization of formulation.The independent variables were oil phase concentration(X1),surfactant concentration(X2),and co-surfactant concentration(X3)while the particle size distribution(Y1),polydispersity index(PDI,Y2)and 10 min drug dissolution(Y3)were the dependent variables.Mel-SMEDDSs were diluted with water to form a light blue microemulsion.The morphology was observed by transmission electron microscopy.The particle size distribution,PDI and Zeta potential were determined by Malvern laser particle size analyzer.The in vitro drug dissolution of meloxicam and Mel-SMEDDSs were compared.The stability of Mel-SMEDDSs was investigated.【Results】The optimized composition of Mel-SMEDDSs was as follows:Peceol TM amount 30 g,Labrasol amount 74 g,Transcutol P amount 17.5 g.Mel-SMEDDSs were dispersed by water to form a spherical microemulsion with uniform size distribution,average particle size(181.7±7.9)nm,PDI(0.251±0.006),and Zeta potential(-10.4±1.4)mV.Compared with meloxicam,MelSMEDDSs could significantly increase the dissolution rate,and the drug dissolution reached(92.4±1.9)%within 10 min.MelSMEDDSs was stable under accelerated conditions for 45 days.【Conclusion】The Mel-SMEDDSs can significantly improve the dissolution rate,which is expected to improve the oral bioavailability,and merits further investigations.