The effect of enzymatic reaction on dissolution rate: theoretical analysis and experimental test.

The dissolution behavior of N-acetylphenylalanine ethyl ester (1) and N-benzoyltyrosine ethyl ester (2) from a rotating disk into aqueous solutions containing the enzyme alpha-chymotrypsin was investigated. The effect of the bulk enzymatic reaction on the dissolution rates is modeled using the continuity equation where the reaction term is considered a constant throughout the reaction zone. Dimensional analysis on the continuity equation defines the important parameter R* = KcatE0h2/(CsD) which is the ratio of the diffusion time to the reaction time. This parameter correctly predicted the fact that the enzymatic reaction had only a slight impact on the dissolution of the highly soluble 1 while the effect on the less soluble 2 was large. Also predicted by R* is the dissolution dependence on the catalytic rate constant. The variation of this rate constant with pH is consistent with the dependence on pH found for the dissolution rate of 2. It is further demonstrated that the decrease in dissolution rate with solubility can be significantly reduced when the dissolving compound is an enzyme substrate. For the two compounds used in this study the dissolution rate decreased with the square root of solubility, as predicted by the theoretical analysis in the presence of enzyme. Other experiments included the variation of the enzyme concentration and the rotational speed of the spinning disk. All experiments were designed to show how R* could correctly predict the relative importance of the convective, diffusive, and reactive processes.