Zhang Feng, Lubach Joseph, Na Watson, Momin Samad
Department of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1920, Austin, Texas 78712.
Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, California 94040.
J Pharm Sci. 2016 Aug;105(8):2386-96. doi: 10.1016/j.xphs.2016.05.020. Epub 2016 Jun 25.
Interaction between Polyox N12K and Carbopol 907 was pH dependent. A hydrogen bond-induced complexation began between pH 5.0 and 6.0 in an aqueous medium, and the interpolymer complex started to precipitate when the pH fell to 4.0. This complex was amorphous with a glass transition temperature of 3.17°C. The molar ratio between ethylene oxide and acrylic acid units in the complex was 1.3:1. About 46% of the COOH groups in Carbopol 907 were H bonded to ether oxygen in Polyox. Theophylline release from tablets containing both polymers was a function of dissolution media pH, due to the pH-dependent interactions. In 0.01 N HCl, an insoluble tablet matrix formed in situ. 93% drug was released over 27 h via Fickian diffusion. In acetate buffer pH 4.0, the insoluble tablet matrix formed in situ disintegrated into tiny gel particles. Gel erosion controlled drug release at pH 4.0. These 2 polymers were unable to complex in a phosphate buffer pH 6.8. Therefore, the tablet matrix dissolved, and drug release followed the anomalous transport mechanism at pH 6.8. The release profiles in an acetate buffer pH 4.0 and phosphate buffer pH 6.8 were statistically same, and a sustained release over 12 h was achieved.
聚氧化乙烯N12K与卡波姆907之间的相互作用取决于pH值。在水介质中，pH值在5.0至6.0之间时开始形成氢键诱导的络合，当pH值降至4.0时，聚合物间络合物开始沉淀。该络合物为无定形，玻璃化转变温度为3.17°C。络合物中环氧乙烷与丙烯酸单元的摩尔比为1.3:1。卡波姆907中约46%的COOH基团与聚氧化乙烯中的醚氧形成氢键。由于pH依赖性相互作用，含有这两种聚合物的片剂中茶碱的释放是溶解介质pH值的函数。在0.01 N HCl中，原位形成不溶性片剂基质。93%的药物在27小时内通过菲克扩散释放。在pH 4.0的醋酸盐缓冲液中，原位形成的不溶性片剂基质崩解成微小的凝胶颗粒。在pH 4.0时，凝胶侵蚀控制药物释放。这两种聚合物在pH 6.8的磷酸盐缓冲液中无法络合。因此，片剂基质溶解，在pH 6.8时药物释放遵循非正规转运机制。在pH 4.0的醋酸盐缓冲液和pH 6.8的磷酸盐缓冲液中的释放曲线在统计学上相同，实现了12小时的持续释放。
