Purpose

The Current Approach:

• Dissolution rate of ionizable compounds is historically treated in a simplified manner based on the solubility of the drug in bulk intestinal fluid at a static pH. Modeling dissolution provides important insight across multiple applications:
  • Formulation Optimization
  • Effect of Proton Pump Inhibitors (PPI)
  • Cross species predictions (dog vs. human)
  • Food Effect Modeling
  • Drug-Drug Interactions
  • Virtual Bioequivalence

The Problem:

• Ionizable drugs and/or excipients can change the pH at their own surface as they dissolve in weak intestinal bicarbonate buffer and gastric fluid leading to inaccurate dissolution predictions when assuming bulk pH.

The Solution:

• Improve existing chemical equilibrium approaches in literature to dynamically calculate the surface pH based on a drugs pKa(s) and important gastrointestinal fluid species.

By James Mullin, Deanna Mudie, Viera Lukacova

AAPS PharmSci 360 2026, October 25-28, 2026, New Orleans, Louisiana