Transient pH film model for in vitro powder dissolution of weakly acidic drugs into buffer: Consideration of surface acidification and comparison to conventional film model

During dissolution, weakly acidic drugs can de-protonate and lower the pH at its dissolving surface, reducing its own solubility at the dissolving surface and dissolution rate. The objective was to derive a simple ionizable drug dissolution film model for weakly acid drug and compare its predictive accuracy to the conventional film dissolution model for particles. Powder dissolution of seven weakly acidic drugs was conducted at various buffer pHs. Drug slurry pH (i.e., surface pH) and slurry solubility, solubility in each bulk medium, and particle sizing were also performed. A film model for ionizable drug dissolution, considering the drug surface solubility, was derived and denoted the transient pH film model. Powder dissolution profiles were predicted from the transient pH film model, and the conventional film model (i.e., z-factor model), which considered drug solubility in bulk but not surface pH. Results show that in vitro drug dissolution was always more accurately predicted from the transient pH film model than the conventional film model. The conventional film model typically over-estimated dissolution, while not considering surface acidification - nor suppressed drug solubility - by the dissolving weakly acid drug. Meanwhile, the transient pH film model neither routinely over-estimated nor routinely under-estimated in vitro dissolution.