Date of Award

January 2015

Degree Type


Degree Name

Doctor of Philosophy (PhD)


Chemical Engineering

First Advisor

Stephen P Beaudoin

Second Advisor

Lynne S Taylor

Committee Member 1

Gintaras V Reklaitis

Committee Member 2

Zoltan K Nagy


Poor aqueous solubility is a major impediment to the oral delivery of over 75% of pharmaceutical compounds currently under development. The bioavailability of these compounds can be enhanced with the use of supersaturating dosage forms, due to their high flux rates across the gastrointestinal tract membrane. However, the success of this strategy hinges on the ability to inhibit crystallization of the supersaturated drug solutions. Polymers can be used to inhibit crystallization and prolong supersaturation, however the mechanisms of polymer inhibition are not yet fully understood. Therefore it is desirable to understand the attributes that render a polymer effective. In this work, the crystal growth rate of a poorly soluble pharmaceutical compound, felodipine, was measured in the presence of various polymers. The growth rate studies were performed using a rotating disk apparatus so that the growth kinetics could be controlled and mathematically modeled. It was found that both polymer ionization state and polymer hydrophobicity greatly impacted polymer effectiveness. Investigation of these systems with atomic force microscopy (AFM) revealed that these properties significantly impacted adsorbed polymer conformation. The polymers that adsorbed in an extended chain conformation were able to achieve a higher degree of surface coverage than those that adsorbed in a coiled globule formation. The surface coverage was found to directly correlate to polymer effectiveness. By modeling this correlation using the Kubota-Mullin model, polymer effectiveness could be predicted when surface coverage was known. This research also assessed the ability of a polymer to impact crystal morphology. It was found that when polymers were present during crystal evolution from an amorphous melt, they were able to impact the size and shape of the resulting crystals. This in turn influenced the rate of crystal growth from supersaturated solutions.