依托泊苷固体自微乳的研制及大鼠体内生物利用度研究

Preparation of Etoposide Solid Self-microemulsifying Drug Delivery System and Its Bioavailability in Rats

目的:制备依托泊苷固体自微乳制剂(SSMEDDS)并研究大鼠灌胃后的药动学行为,提高依托泊苷口服生物利用度。方法:通过相图法得到相应的自乳化区域,并以自乳化速率、粒径及溶解度等作为考察指标筛选处方,寻找出最佳处方配比;采用溶出度实验测定依托泊苷固体自微乳的体外溶出度等理化参数;考察了依托泊苷固体自微乳制剂、市售制剂和原料药混悬液经大鼠灌胃给药后的药动学行为。结果:依托泊苷自微乳的平均粒径为(21.8±1.5)nm,且固体自微乳制剂45 min溶出95%以上,同时药动学数据显示依托泊苷固体自微乳、原料药和市售制剂的AUC分别为12.20、8.25、10.49 mg.h.L-1。结论:VP-16制成固体自微乳制剂后的AUC略高于市售制剂,且大大提高了依托泊苷原料药的生物利用度。

Objective： To study the Solid Self-micro-emulsifying Drug Delivery System（SSMEDDS） of Etoposide（VP-16） and its pharmacokinetic characteristics in rats to improve its bioavailability. Methods： The recipe of SSMEDDS of VP-16 was optimized by studying the pseudoternary phase diagram,the self-emulsifying rate and the particle size.Dissolution rates of VP-16 loaded SSMEDDS were investigated in order to validate the efficiency.The plasma concentrations of VP-16 were detected at the preplanned intervals following intragastric administration of a single dose of 20 mg·kg-1 VP-16 to rats.The plasma concentration of VP-16 was determined by HPLC.Results： After dilution of the developed VP-16 SSMEDDS with water,the size of the micro-emulsion was determined to be（21.8±1.5） nm.The preparation of VP-16 SSMEDDS dissoluted more than 95% at 45 min.AUC were 12.20,8.25 and 10.49 mg·h·L-1,respectively,for VP-16 SSMEDDS,its raw material and commercial preparation given to rats.Conclusion： There exist significant improvements in the bioavailability of VP-16 in SSMEDDS.