罗替戈汀微乳凝胶的制备与体内外评价

Preparation of rotigotine microemulsion gel and its in vitro and in vivo evaluation

目的:制备一种罗替戈汀微乳凝胶剂,达到促进药物经皮吸收和降低皮肤局部反应的目的。方法:通过伪三元相图法得到微乳区,Box-behnken设计法得到了粒径小、黏度小的微乳处方,并考察了罗替戈汀微乳的体外经皮渗透特性、粒径、形态和稳定性。上市的贴剂作为对照,考察了罗替戈汀微乳凝胶在大鼠腹部皮肤给药后的生物利用度和皮肤局部的敏感性。结果:罗替戈汀微乳凝胶各组分的质量百分含量:labrafil为6.4%,Cremphor RH40为19.2%,Transcutol HP为6.4%,水为68%,罗替戈汀为1%,卡波姆1342为1%。与上市贴剂相对生物利用度为(91.36±9.68)%,具有较小的皮肤刺激性。结论:罗替戈汀微乳凝胶对皮肤作用温和,有望成为一种新型的经皮给药系统。

Objective： To develop a microemulsion-based hydrogel for transdermal rotigotine delivery with improved permeation property and lower local reactions. Methods： Microemulsion area was obtained by pseudo-ternary phase diagrams. The proportion of each component of microemulsion was determined by a Box-behnken design to achieve smaller particle size and lower viscosity. The in vitro penetration performance, particle size, shape and stability of rotigotine microemulsion were then investigated. In vivo bioavailability and site reactions of rotigotine microemulsin gel were also tested in comparison with the marketed patch. Results： The composition of the rotigotine microemulsion gel was 6.4% , 19.2% labrafil cremphor RH40, 6.4% transcutol HP, 68% water, 1% rotigotine and 1% carbopol 1342. The microemulsion gel had a relative bioavailability of （91.36 ＋9.68）% and lower local reactions in application site compared with the marketed patch. Conclusion： This product can improve patient compliance and has broad marketability.