In Vivo Predictive Dissolution: Comparing the Effect of Bicarbonate and Phosphate Buffer on the Dissolution of Weak Acids and Weak Bases

Bicarbonate is the main buffer in the small intestine and it is well known that buffer properties such as pK_a can affect the dissolution rate of ionizable drugs. However, bicarbonate buffer is complicated to work with experimentally. Finding a suitable substitute for bicarbonate buffer may provide a way to perform more physiologically relevant dissolution tests. The dissolution of weak acid and weak base drugs was conducted in bicarbonate and phosphate buffer using rotating disk dissolution methodology. Experimental results were compared with the predicted results using the film model approach of (Mooney K, Mintun M, Himmelstein K, Stella V. 1981. J Pharm Sci 70(1):22–32) based on equilibrium assumptions as well as a model accounting for the slow hydration reaction, CO₂ + H₂O → H₂CO₃. Assuming carbonic acid is irreversible in the dehydration direction: CO₂ + H₂O ← H₂CO₃, the transport analysis can …