(178c) Polymer Inhibition of Crystal Growth for Improved Drug Solubility

A large percentage of active pharmaceutical ingredients (APIs) in the drug development pipeline demonstrate poor aqueous solubility as crystalline solid forms. This poses a problem for oral therapeutics due to decreased bioavailability. Utilizing the amorphous form of the drug rather than the crystalline form is an effective method to alleviate solubility issues, due to its greater overall free energy. Much emphasis has been placed on methods to stabilize the inherently unstable amorphous form and prevent crystallization. One such method utilizes polymers to act as a mechanical barrier, occupying growth sites. The effectiveness of this method, however, varies for each polymer-drug combination.

In this work, we study polymer inhibition of crystal growth of the drug felodipine in solution. We use a rotating disc apparatus (RDA) to eliminate diffusion effects, which allows us to study growth kinetics controlled purely by integration at growth sites. We then use atomic force microscopy (AFM) to quantify the amount of adsorbed polymer, as well as to document its adsorbed conformation on solid felodipine. These results reveal insights into the mechanisms by which polymers can effectively inhibit crystal growth.