2018 AIChE Annual Meeting

(200aj) Unique Polymorph and Amorphous Dispersion Formation of Suberic Acid Using Monodisperse Droplet Evaporation

Authors

Snyder, R. C. - Presenter, Bucknell University
Karakis, V., Bucknell University
Ditmar, E., Bucknell University
Vostal, K. R., Bucknell University
In order to effectively deliver an Active Pharmaceutical Ingredient (API), pharmaceutical companies rely on specific particle properties including size, morphology, and structure to achieve desirable drug performance. The structure in particular, be it one of multiple crystalline polymorphs or an amorphous form, directly impacts the solubility of pharmaceutical compounds. As pharmaceutical molecules become ever more complex, their solubility in the body and resulting bioavailability is often decreased. Therefore, methods to understand the formation of different crystalline polymorphs, as well as amorphous dispersions of organic molecular systems is important for pharmaceutical development.

In this work, we use a monodisperse droplet evaporation process technology to form polymorphs that are not obtained with identical chemistry using other formation processes. Monodisperse droplet evaporation is achieved by use of a Vibrating Orifice Aerosol Generator (VOAG), which creates droplets of solution that are well dispersed from one another allowing for the solvent to rapidly evaporate at room temperature. The rapid droplet evaporation leads to high supersaturations, which drives a potential for formation of metastable polymorphs and amorphous dispersions. Suberic acid is the primary small molecule considered in this work first as a standalone system in multiple solvents to study suberic polymorphism. Secondly, it is mixed with polyvinylpyrrolidone (PVP) and dissolved in isopropanol to study the formation of amorphous dispersions. Our results demonstrate the ability of the VOAG to lead to a previously unreported polymorph of suberic acid. Further, we form a variety of amorphous dispersions for which we determine the dispersion stability as well as suberic acid solubility estimates in PVP.