Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
Mol Pharm. 2013 Jun 3;10(6):2283-90. doi: 10.1021/mp3006209. Epub 2013 May 8.
Much interest has been expressed in this work on the role of water diffusivity in the release media as a new parameter for predicting drug release. NMR was used to measure water diffusivity in different media varying in their osmolality and viscosity. Water self-diffusion coefficients in sucrose, sodium chloride, and polymeric hydroxypropyl methylcellulose (HPMC) solutions were correlated with water uptake, disintegration, and drug release rates from trospium chloride immediate release tablets. The water diffusivity in sucrose solutions was significantly reduced compared to polymeric HPMC and molecular sodium chloride solutions. Water diffusivity was found to be a function of sucrose concentration in the media. Dosage form disintegration and drug release was to be affected by water diffusivity in these systems. This observation can be explained by hydrogen bonding formation between sugar molecules, an effect which was not expressed in sodium chloride solutions of equal osmolality. Water diffusivity and not media osmolality in general need to be considered to predict the effect of disintegration and dissolution media on drug release. Understanding the relevance of water diffusivity for disintegration and dissolution will lead to better parametrization of dosage form behavior in gastrointestinal (GI) aqueous and semisolid media.
人们对这项工作中水分子扩散系数在释放介质中的作用表现出极大的兴趣，认为它是预测药物释放的一个新参数。本研究采用 NMR 技术测量了在渗透压和黏度不同的多种释放介质中的水分子扩散系数。从曲司氯铵速释片的水摄取量、崩解和药物释放速率方面，对蔗糖、氯化钠和高分子羟丙基甲基纤维素（HPMC）溶液中的水自扩散系数进行了相关性研究。与高分子 HPMC 和分子氯化钠溶液相比，蔗糖溶液中的水分子扩散系数明显降低。在这些介质中，水分子扩散系数是蔗糖浓度的函数。水扩散系数会影响这些体系中制剂的崩解和药物释放。这种观察结果可以用糖分子之间形成氢键来解释，而在渗透压相等的氯化钠溶液中则没有表现出这种效应。需要考虑水的扩散系数而不是介质的渗透压，以便预测崩解和溶解介质对药物释放的影响。了解水扩散系数对崩解和溶解的相关性，将有助于更好地描述胃肠道（GI）水相和半固态介质中制剂行为的参数化。
