Date of Award

January 2016

Degree Type


Degree Name

Doctor of Philosophy (PhD)


Industrial and Physical Pharmacy

First Advisor

Stephen R. Byrn

Committee Member 1

Lynne S. Taylor

Committee Member 2

Rodolfo Pinal

Committee Member 3

Gregory T. Knipp

Committee Member 4

Patrick J. Marsac


Most drug substances are reported to be either weak acids or weak bases. Hence, acid-base reactions are commonly observed in pharmaceutical systems with samples including salts, amorphous solid dispersions, and in formulated products. Salt formation of active pharmaceutical ingredients (APIs) is widely recognized as one of the most commonly used approaches to modify the solubility and dissolution rate. Formulating poorly water-soluble weak acids or weak bases into salts can not only increase bioavailability, but also improve the stability and manufacturability of APIs by changing their solid-state properties. However, from a formulation perspective, acid-base reactions might occur between APIs and ionizable excipients, which would induce deleterious form conversions or chemical degradation of the APIs during storage or manufacturing. Therefore, understanding the fundamentals of acid-base reactions is critical to design a robust formulation and to avoid drug-excipients incompatibility issues in multicomponent pharmaceutical products.