盐酸氟西汀微乳的制备及其离体大鼠透皮作用研究

Preparation of Fluxetine Hydrochloride Microemulsion and Its Percutaneous Penetration on Rats in Vitro

目的:制备盐酸氟西汀(FLU)微乳并考察其对离体大鼠的透皮能力。方法:筛选空白微乳中表面活性剂、助表面活性剂、油相等的组成及质量比,制备FLU微乳并考察其粒径及分布等指标;用改进的Franz扩散池研究微乳的透皮速率,考察油相含量、混合表面活性剂含量及载药量对透皮吸收的影响以优化处方并进行验证试验。结果:空白微乳组成为肉豆蔻酸异丙酯(IPM)/聚乙二醇羟硬脂酸酯15(SolutolSH15)/聚乙二醇(PEG)400/水;样品平均粒径为44.6nm,呈正态分布,多分散系数为0.317;最优处方为FLU/IPM/SolutolSH15/PEG400/水(1∶9∶20∶20∶39),验证试验中3批样品稳态透皮速率平均值为(128.96±0.32)μg·cm-2·h-1。结论:所制FLU微乳有较强的透皮能力,可进一步开发为FLU的新型透皮给药制剂。

OBJECTIVE： To prepare fluxetine hydrochloride （FLU） microemulsion, and to investigate in vitro transdermal delivery ability of it in isolated rat. METHODS： The microemulsion was prepared by screening the constituent and proportion of surfactant, cosurfactant, oil phase, etc. The particle size and distribution of microemulsion were investigated. The permeation rate of microemulsion was determined using Franz diffusion cell. The effects of the content of oil phase and mixed surfactant and the drug-loading amount on the transdermal delivery ability of it were investigated to optimize formula. Verification test was also carried out. RESULTS： The optimized formulation of blank microemulsion was made up of isopropyl myristate （IPM）, Solutol SH15, PEG400 and water （1 ∶ 9 ∶ 20 ∶ 20 ∶ 39）. Mean particle size of samples was 44.6 nm and showed statistically normal distribution. Polydispersity index was 0.317. The permeation rate of 3 batches of samples was （128.96±0.32）g·cm-2·h-1. CONCLUSION： Prepared FLU microemulsion has high permeation rate, which may be a promising vehicle for the transdermal delivery of FLU.