Dissolution of ionizable drugs into unbuffered solution: a comprehensive model for mass transport and reaction in the...

A model has been developed to describe the mass transport and reaction of ionizable compounds where mass transfer is caused by convection and diffusion from a rotating disk. Dissolution rates of benzoic acid, 2-naphthoic acid, and indomethacin in aqueous solutions of high ionic strength (I = 0.5 with potassium chloride) at 25 degrees C were investigated. The model includes the effects of diffusion, convection, and simultaneous acid/base reaction at all points in the region adjacent to the dissolving solid. The solution of the transport equations is obtained numerically with an iterative algorithm which uses (a) closure of all material balances and (b) equilibria at the solid/liquid surface as constraints. The model solution yields both the flux of the dissolving acid and the concentration profile of each component. Reduced values of all reaction rate constants are used in the region adjacent to the dissolving surface to allow convergence of the computation. Although nonequilibrium concentration values are calculated, it is shown that the theoretical dissolution rate determined as the solution of the model is insensitive to the magnitude of the rate constants as their maximum useable values are approached. Comparisons of the model results with experimentally determined fluxes show close agreement and confirm that the transport mechanisms in the model formulation are consistent with the measured values. Further, the inclusion of convection allows accurate calculations without utilization of an arbitrary boundary layer thickness. Accurate dissolution rates can be determined using this technique under a wide range of conditions, except at low pH.