Evaluating Drug Salt Dissolution and Precipitation Processes for Rational Formulation Strategies

Purpose. The salt form of an API (active pharmaceutical ingredient) may dissolve, partially or completely, to transient concentrations above equilibrium solubility levels. The supersaturated solution may then precipitate as the free acid/base, sometimes coating the remaining input API or formulation, thus significantly modifying the subsequent dissolution rate. The timeframe of supersaturation and potential precipitation events may have profound effects on bioavailability in vivo. The aim of this study was to develop a practical and predictive in vitro powder and formulation dissolution method to monitor dissolution and concomitant precipitation processes in biorelevant media. Conclusions. This novel in situ monitoring approach to in vitro powder and formulation dissolution/precipitation can provide a fundamental understanding of processes that may be relevant in vivo providing rational approach to formulation design and development.