维生素D3自微乳化制剂的制备与体外评价

Preparation and in vitro Evaluation of Vitamin D3 Self-microemulsifying System

在溶解度试验和伪三元相图基础上,以自乳化时间、粒径、ζ电位为评价指标,采用星点设计-效应面法优化维生素D3自微乳化制剂的处方,得到的最优处方组成为油酸乙酯、聚氧乙烯40氢化蓖麻油和1,2-丙二醇,质量比为0.2∶0.53∶0.27。该自微乳体系中加入50 mg/g的维生素D3,再经37℃、50倍的蒸馏水稀释乳化后可形成淡蓝色的澄清透明溶液,其中微乳的平均粒径为(30.90±0.05)nm,ζ电位为(-16.28±0.09)mV,多分散系数为0.08±0.02。该维生素D3自微乳化制剂灌装于胶囊中后在pH 6.8磷酸盐缓冲液中的溶出速度和程度显著高于灌装原料药的胶囊。初步稳定性试验显示该自微乳化体系较稳定。

Based on the results of solubility test and pseudo-ternary phase diagrams,the formulation composition of self-microemusifying drug delivery system(SMEDDS)loaded with vitamin D3 were furtherly optimized by central composite design-response surface methodology with self-emulsifying time,particle size andζpotential as the evaluation indexes.The results showed that the optimal blank SMEDDS was composed of ethyl oleate,polyoxyl(40)hydrogenated castor oil and 1,2-propanediol with a mass ratio of 0.2∶0.53∶0.27.After adding 50 mg/g of vitamin D3 and diluting with 50 times volume of distilled water at 37℃,the system was self-emulsified to form a transparent solution with light blue opalescence.The average particle size,polydispersity andζpotential of the microemulsion were(30.90±0.05)nm,0.08±0.02 and(-16.28±0.09)mV,respectively.The dissolution rate and degree of vitamin D3 from the optimal SMEDDS in capsules were significantly higher than those of bulk drug capsules.The preliminary stability test showed that the SMEDDS was rather stable.