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羧酸的溶解动力学I:非缓冲条件下pH值的影响

Dissolution kinetics of carboxylic acids I: effect of pH under unbuffered conditions.

作者信息

Mooney K G, Mintun M A, Himmelstein K J, Stella V J

出版信息

J Pharm Sci. 1981 Jan;70(1):13-22. doi: 10.1002/jps.2600700103.

Abstract

The dissolution behavior of benzoic acid, 2-naphthoic acid, and indomethacin from rotating compressed disks into aqueous solutions of constant ionic strength (mu = 0.5 with potassium chloride) at 25 degrees was investigated. The pH of the bulk aqueous medium was maintained during dissolution by means of a pH-stat apparatus. A model for the initial steady-state dissolution rate of a monoprotic carboxylic acid was derived from Fick's second law of diffusion. This model assumed that diffusion-controlled mass transport and simple, instantaneously established reaction equilibria existed across a postulated diffusion layer. Using previously determined intrinsic solubilities, pKa values, and diffusion coefficients, the model was found to predict the dissolution rates of these acids accurately as a function of the bulk solution pH. Hydroxide ion and water were the only reactive base species present in the bulk solution. The concentration profiles of all of the species across the diffusion layer were generated for a given bulk pH. Furthermore, the model generated values for the pH profile within the microclimate of the diffusion layer and the pH at the solid-solution boundary.

摘要

研究了苯甲酸、2-萘甲酸和吲哚美辛从旋转压缩盘在25℃下进入具有恒定离子强度(μ = 0.5,含氯化钾)的水溶液中的溶解行为。在溶解过程中,通过pH计装置维持本体水介质的pH值。从菲克第二扩散定律推导出了一元羧酸初始稳态溶解速率的模型。该模型假设在假定的扩散层中存在扩散控制的质量传输和简单的、瞬时建立的反应平衡。利用先前测定的固有溶解度、pKa值和扩散系数,发现该模型能够准确预测这些酸的溶解速率与本体溶液pH值的函数关系。氢氧根离子和水是本体溶液中仅有的反应性碱物种。针对给定的本体pH值,生成了所有物种在扩散层中的浓度分布。此外,该模型还生成了扩散层微环境内的pH分布值以及固液边界处的pH值。

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