AAPS PharmSciTech. 2014 Feb;15(1):1-10. doi: 10.1208/s12249-013-0004-8.
Providing pH-independent oral release of weakly basic drugs with conventional matrix tablets can be challenging because of the pH-dependent solubility characteristics of the drugs and the changing pH environment along the gastrointestinal tract. The aim of the present study was to use a hydrophobic polymer to overcome the issue of pH-dependent release of weakly basic model drug verapamil hydrochloride from matrix tablets without the use of organic buffers in the matrix formulations. Silicone pressure-sensitive adhesive (PSA) polymer was evaluated because of its unique properties of low surface energy, hydrophobicity, low glass transition temperature, high electrical resistance, and barrier to hydrogen ion diffusion. Drug release, hydrogen ion diffusion, tablet contact angle, and internal tablet microenvironment pH with matrix tablets prepared using PSA were compared with those using water-insoluble ethyl cellulose (EC). Silicone PSA films showed higher resistance to hydrogen ion diffusion compared with EC films. Verapamil hydrochloride tablets prepared using silicone PSA showed higher hydrophobicity and lower water uptake than EC tablets. Silicone PSA tablets also showed pH-independent release of verapamil and decreased in dimensions during drug dissolution. By contrast, verapamil hydrochloride tablets prepared using EC did not achieve pH-independent release.
使用常规基质片剂为弱碱性药物提供 pH 非依赖性口服释放可能具有挑战性，因为药物的 pH 依赖性溶解度特征以及胃肠道中 pH 环境的变化。本研究的目的是使用疏水性聚合物来克服弱碱性模型药物盐酸维拉帕米从基质片剂中 pH 依赖性释放的问题，而无需在基质配方中使用有机缓冲剂。硅酮压敏胶 (PSA) 聚合物因其低表面能、疏水性、低玻璃化转变温度、高电阻和氢离子扩散屏障等独特性质而被评估。使用 PSA 制备的基质片剂的药物释放、氢离子扩散、片剂接触角和内部片剂微环境 pH 与使用不溶于水的乙基纤维素 (EC) 制备的片剂进行了比较。硅酮 PSA 薄膜对氢离子的扩散阻力高于 EC 薄膜。与 EC 片剂相比，使用硅酮 PSA 制备的盐酸维拉帕米片剂表现出更高的疏水性和更低的吸水量。硅酮 PSA 片剂还表现出盐酸维拉帕米的 pH 非依赖性释放，并在药物溶解过程中尺寸减小。相比之下，使用 EC 制备的盐酸维拉帕米片剂未能实现 pH 非依赖性释放。
