川丁特罗贴剂的设计及分子机制研究

目的 采用离子对与促透剂联合应用的促透策略，设计一种经皮透过性良好的川丁特罗贴剂，用于支气管哮喘的治疗。方法 首先采用有机溶媒挥散法制备川丁特罗经皮吸收贴剂，以Wistar大鼠皮肤为模型，采用单因素考察法在体外经皮透过试验中考察离子对与促透剂的联用对川丁特罗经皮透过行为的影响并优选贴剂处方。通过贴剂体外释放试验和红外光谱试验，探讨离子对及促透剂对川丁特罗经皮透过行为的影响及分子机制。结果 贴剂的优选处方为川丁特罗-对氨基苯甲酸为主药，载药量为5%，DURO-TAK^®87-4098为压敏胶基质，8%聚甘油油酸酯为促透剂。离子对的形成增加了川丁特罗的皮肤渗透性，而聚甘油油酸酯的加入对川丁特罗从贴剂中的释放和川丁特罗皮肤透过均有促进作用，2个技术的联用增加了川丁特罗的皮肤累积透过量。结论 本研究通过采用离子对与促透剂联合应用的策略，成功设计了川丁特罗压敏胶分散型贴剂，并从释放和经皮吸收2方面探讨了离子对和促透剂的作用机制，为开发川丁特罗贴剂提供参考。

Design and Molecular Mechanism Evaluation of Trantinterol Patch

OBJECTIVE To design a transdermal patch of trantinterol with good skin permeability for the treatment of bronchial asthma by adopting the combination of ionpair and permeation enhancer strategy. METHODS The transdermal patch of trantinterol was prepared by the organic solvent evaperation method, and the full thickness skin of Wistar rat was used as a model to investigate the effect of ionpair and permeation enhancer on the skin permeation behavior of trantinterol by single factor investigation method in the in vitro skin permeation study. The molecular mechanism of ionpair and permeation enhancer on the skin permeation behavior of trantinterol were investigated through the in vitro drug release experiments and FTIR experiments. RESULTS The optimized formulation of the patch were the ionpair of trantinterol-p-aminobenzoic acid as the main drug, drug loading of 5%, DURO-TAK^®87-4098 as the pressure sensitive adhesive, and 8% polyglycerol oleate (POCC) as the permeation enhancer. The formation of ionpair increased the skin permeation of trantinterol, and the addition of POCC promoted both the release process of trantinterol from the patch and the skin permeation process. The combined application of the technologies increased the cumulative skin permeation of trantinterol. CONCLUSION In this study, by adopting both ionpair and permeation enhancer strategys, a drug-in-adhesive patch of trantinterol is successfully designed, and the molecular mechanism of ionpair and permeation enhancer is discussed from the two processes of release and percutaneous absorption. This study provides a reference for the development of trantinterol transdermal patch.