Ching Ai Ling, Liew Celine Valeria, Chan Lai Wah, Heng Paul Wan Sia
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Eur J Pharm Sci. 2008 Apr 23;33(4-5):361-70. doi: 10.1016/j.ejps.2008.01.007. Epub 2008 Feb 1.
Lamination of alginate matrix tablet at acidic pH can compromise its function as a sustained release carrier. This phenomenon is associated with the conversion of sodium alginate to alginic acid. An innovative approach for controlling the release of a highly water-soluble drug from such matrices is presented in this paper. Inclusion of pH-modifiers was employed to raise the micro-environmental pH within matrices undergoing dissolution at gastric pH. The changes in micro-environmental pH of hydrating alginate matrices were visualized with the aid of a pH-indicator and subsequently quantified using image analysis. Transient elevation in micro-environmental pH impeded alginate protonation and minimized or prevented matrix lamination, contributing to preservation of drug diffusion barrier. Significant reduction in the rate of drug release at pH 1.2 was achieved in the presence of such additives. The action of pH-modifiers was synergistically enhanced in the presence of a carbon dioxide barrier formed by effervescing sodium bicarbonate, reducing drug release in the acidic medium from 60 to 20%. Further insight into the influence of lamination on drug release from alginate compacts was given.
在酸性pH值下藻酸盐基质片剂的分层会损害其作为缓释载体的功能。这种现象与海藻酸钠向海藻酸的转化有关。本文提出了一种从这类基质中控制高水溶性药物释放的创新方法。采用加入pH调节剂的方法来提高在胃pH值下溶解的基质内的微环境pH值。借助pH指示剂观察水合藻酸盐基质微环境pH值的变化，随后使用图像分析进行量化。微环境pH值的短暂升高阻碍了藻酸盐的质子化，并使基质分层最小化或得到防止，有助于保留药物扩散屏障。在存在这类添加剂的情况下，在pH 1.2时药物释放速率显著降低。在由泡腾碳酸氢钠形成的二氧化碳屏障存在下，pH调节剂的作用得到协同增强，使酸性介质中的药物释放从60%降低到20%。进一步深入了解了分层对藻酸盐压片药物释放的影响。
