Transient pH film model for in vitro powder dissolution of weakly basic drugs into buffer and comparison to...

The dissolution of ionizable drugs is critically influenced by the pH of the microenvironment at the solid-liquid interface, which in part can be impacted by the dissolving drug itself. For weak bases, dissolution may increase surface pH, thereby possibly reducing local solubility and slowing the dissolution rate. The objective was to apply the previously described transient pH film model to 11 weakly basic drugs and compare its predictive accuracy to the conventional film dissolution model for particles. Across the 11 drugs, sixty powder dissolution conditions were tested using 50 mM phosphate buffer. Particle sizing, pH-solubility profiles, and surface pH calculations were also performed. Powder dissolution profiles were predicted from the transient pH film model and the conventional film model (i.e., z-factor model). Results show that, when experimental conditions anticipate drug ionization to increase surface pH and decrease surface drug solubility compared to bulk (i.e., about half the time here), in vitro drug dissolution was almost always more accurately predicted from the transient pH film model than the conventional film model. Otherwise, conventional film model was satisfactory since particle surface pH did not increase, or at least did not decrease surface drug solubility.