An Approach for the Prediction of the Intrinsic Dissolution Rates of Drugs under Unbuffed Conditions

Abstract

Predicted intrinsic dissolution rates were obtained under unbuffered conditions for ionizable and unionizable drugs employing a simple approach based on the diffusion layer theory. These rates correlated well with experimentally determined values for Cromakalim, Diproteverine HC1 and Ephedrine thereby substantiating the applicability of the approach for these molecules. For ionizable molecules, the pH at the surface of the dissolving particles rather than the bulk pH, in addition to the other parameters of the Noyes-Whitney equation, determine the intrinsic dissolution rates. For unionizable drugs, the rate is primarily determined by the original Noyes-Whitney equation. The model could be employed in the selection of an appropriate chemical or physical form of a drug for development.