ABSTRACT
This study investigated the possible effects of simultaneous, noninstantaneous, reversible chemical ionization of carbon acids on the dissolution of a typical pharmaceutical carbon acid, phenylbutazone, and its deutero analog. The dissolution rate versus pH profile for phenylbutazone was consistent with phenylbutazone acting as if it were an acid where the ionization can be considered instantaneous. In view of the dissolution behavior of phenylbutazone under various conditions, it is unlikely that the noninstantaneous ionization kinetics demonstrated for this compound play a major role in determining the dissolution rate, either in vitro or in vivo, since the average residence time in a typical aqueous diffusion layer for phenylbutazone dissolution is longer than the reaction time for its ionization. Slowing the reaction time with a primary isotope effect by deuterium substitution for the ionizable proton caused significant deviation from classical behavior for d-phenylbutazone.
