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  • Title: Dissolution kinetics of carboxylic acids I: effect of pH under unbuffered conditions.
    Author: Mooney KG, Mintun MA, Himmelstein KJ, Stella VJ.
    Journal: J Pharm Sci; 1981 Jan; 70(1):13-22. PubMed ID: 7229925.
    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.
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