Unleashing Bioavailability: Particle Size, Salt Form, and the Race Against Disproportionation

Active Pharmaceutical Ingredients (APIs) have a limited window to dissolve as they pass through the gastrointestinal tract, crucial for their absorption and effectiveness. Enhancing the dissolution rate of APIs, particularly those with poor solubility, is thus key for improving their bioavailability [1]. Two established strategies to achieve dissolution rate enhancement are salt formation and particle size reduction. Salt formation increases the aqueous solubility, particularly for APIs derived from weak acids or bases. Reducing 
the particle size increases the surface area available for dissolution, thereby accelerating the dissolution rate.

A combination of salt formation and particle size reduction could synergistically enhance API bioavailability. 

The SPA® platform was used to measure the solubility and IDR of the model pharmaceutical HCl salt in Fasted State Simulated Intestinal Fluid (FaSSIF V1), replicating the conditions of the small intestine where most absorption occurs. FaSSIF V1 was prepared according to the procedure at Biorelevant.com.

The strategic implementation of particle size reduction for a poorly soluble API HCl salt was successfully demonstrated to achieve complete dissolution before the onset of disproportionation.