压敏胶贴剂中川芎嗪的结晶抑制及经皮动力学研究

 目的研制一种川芎嗪的聚丙烯酸酯压敏胶贴剂。方法以聚丙烯酸酯压敏胶为基质设计不同的处方,考察了几种高分子添加剂对川芎嗪在聚丙烯酸酯压敏胶基质中结晶的影响;通过水平透皮扩散池测定川芎嗪贴剂中川芎嗪透过SD大鼠背部皮肤的渗透速率,研究不同高分子添加剂、皮肤透过促进剂(PE)以及聚乙烯吡咯烷酮(PVPK-30)含量对经皮渗透速率的影响。结果PVPK-30对川芎嗪结晶有较强的抑制作用,在含有质量分数为7.5%PVPK-30的基质中加入质量分数为20%卡毕醇可以达到明显的促渗效果,经皮渗透速率约300μg·cm^-2·h^-1。结论按优选处方制得的川芎嗪骨架贴剂,通过体外透过实验结果推测可达到治疗血药浓度的要求。

Studies on Inhibition of Crystallization and in vitro Percutaneous Absorption of Tetramethylpyrazine Transdermal Delivery system

OBJECTIVE To develop a transdermal delivery system(TDS)for tetramethylpyrazine(TMP). METHODS TMP was incorporated with polyacrylate adhesive.The effect of additives on the crystallization of TMP in polyacrylate adhesive matrix was investigated.The permeation of TMP through SD rat dorsal skin was studied and the influence of different factors(type of adhesive, presence of additives, enhancers and amount of PVPK-30)was investigated. RESULTS PVPK-30 was found to be an effective crystallization inhibitor. The optimized TDS, which was a Duro-Tak 87-2677 based formulation with 20% transcutol and 7.5% PVPK-30 as additives, showed a percutaneous flux of 300 μg·cm^-2·h^-1.CONCLUSION The in vitro percutaneous results indicate that an optimized TDS can supply a steady state flux for its therapeutic plasma levels in an appropriate size.