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基于苯乙烯-异戊二烯-苯乙烯嵌段共聚物的贴剂中药物释放曲线的评价:嵌段结构和增塑剂的影响。

Evaluation of drug release profile from patches based on styrene-isoprene-styrene block copolymer: the effect of block structure and plasticizer.

机构信息

Department of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.

出版信息

AAPS PharmSciTech. 2012 Jun;13(2):556-67. doi: 10.1208/s12249-012-9778-3. Epub 2012 Apr 3.

Abstract

We prepared pressure-sensitive adhesive (PSA) patches based on styrene-isoprene-styrene (SIS) thermoplastic elastomer using hot-melt coating method. The liquid paraffine is added in the PSA matrices as a plasticizer to moderate the PSA properties. Three drugs, methyl salicylate, capsaicin, and diphenhydramine hydrochloride are selected as model drugs. The Fourier transform infrared spectroscopy, differential scanning calorimetry test, and wide-angle X-ray diffraction test indicate a good compatibility between drugs and matrices. Peppas equation is used to describe drug release profile. Different drug-matrix absorption, as indicative of drug-matrix interaction, accounts for the variation in release profiles of different drugs. Furthermore, atomic force microscopy and rheological studies of the PSA samples are performed to investigate the effect of SIS structure and plasticizer of PSA on drug release behaviors. For methyl salicylate and capsaicin, drug diffusion in the PSA matrices is the main factor controlled by the release kinetic constant k. The high [SI] diblock content and high plasticizer amount in matrix provide the PSA with a homogeneous and soften microstructure, resulting in a high diffusion rate. But for water-soluble drugs such as diphenhydramine hydrochloride, the release rate is governed by water penetration with the competition from diffusion mechanisms.

摘要

我们使用热熔涂覆法,基于苯乙烯-异戊二烯-苯乙烯(SIS)热塑性弹性体,制备了压敏胶(PSA)贴片。液体石蜡作为增塑剂添加到 PSA 基质中,以调节 PSA 的性能。选择三种药物,即水杨酸甲酯、辣椒素和盐酸苯海拉明作为模型药物。傅里叶变换红外光谱、差示扫描量热法和广角 X 射线衍射试验表明,药物与基质之间具有良好的相容性。Peppas 方程用于描述药物释放曲线。不同的药物-基质吸收,表明药物-基质相互作用的不同,导致了不同药物释放曲线的变化。此外,还对 PSA 样品进行原子力显微镜和流变学研究,以研究 SIS 结构和 PSA 中增塑剂对药物释放行为的影响。对于水杨酸甲酯和辣椒素,药物在 PSA 基质中的扩散是由释放动力学常数 k 控制的主要因素。基质中高的 [SI] 二嵌段含量和高增塑剂含量提供了 PSA 均匀且软化的微观结构,从而导致高扩散速率。但是对于水溶性药物,如盐酸苯海拉明,释放速率受到水渗透的控制,同时受到扩散机制的竞争。

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