倍他司汀经皮吸收贴剂的处方优化

Formulation optimization of betahistine transdermal patch

目的制备倍他司汀经皮吸收贴剂,以便更好地用于美尼尔综合征的治疗。方法采用有机溶媒挥散法制备倍他司汀压敏胶分散型贴剂;通过体外经皮渗透实验进行处方优化,实验装置为水平双室扩散池,以离体兔皮为通透屏障,采用控制单因素变量法筛选贴剂系统中的压敏胶、背衬层以及促透剂;通过家兔皮肤刺激性实验初步考察贴剂的安全性。结果倍他司汀贴剂中采用Duro-Tak~87-4098压敏胶为基质,Co Tran^(TM) 9722为背衬层,载入l-薄荷醇作为促透剂。所制备的倍他司汀贴剂无皮肤刺激性。结论处方优化后的倍他司汀贴剂体外12 h经皮累积渗透量显著增加,为倍他司汀经皮吸收贴剂的后续研究提供了一定的实验依据。

Objective The aim of the present study was to prepare betahistine patches in order to cure Ménière's disease more effectively. Methods In the study, organic solvent evaporation technique was used to prepare the drug-in-adhesive patch of betahistine. Pressure sensitive adhesives, backing films and chemical enhancers of the betahistine patch were screened through in vitro permeation experiments, which were carried out by using side-by-side horizontal diffusion cells through excised rabbit skin. Skin irritation experiments were done in rabbit. Result Based on the results of above-mentioned single-factor screening tests, the optimized formulation of betahistine patch was determined as Duro-Tak~87-4098 pressure sensitive adhesive, Co Tran^(TM)9722 backing film and l-menthol as chemical enhancer. The result of the skin irritation experiment revealed that the BH patch showed no irritation. Conclusion The optimized betahistine patch showed increased permeation behavior. This study provides basis for the follow-up research.