Date of Thesis
An Active Pharmaceutical Ingredient (API) is a compound that is usually mixed with one or more additives to form a pill that is orally consumed as a drug. The specific crystal form of an API that is present in the pill has important particle properties, such as size, morphology, and internal structure that can affect the performance of a drug. Organic molecules are often used to model the behavior of APIs and this thesis uses a monodisperse droplet evaporation method to determine the morphology, internal structure, and phase transformation kinetics of particles formed from the organic molecule of suberic acid and various compositions of suberic acid and polyvinylpyrillodone (PVP) mixtures. Suberic acid particles formed via droplet evaporation from a Vibrating Orifice Aerosol Generator (VOAG) produce a mix of the alpha and gamma polymorph. This thesis corroborates previous work demonstrating this unique formation of the gamma polymorph. Over time the gamma polymorph transitions to the more stable alpha polymorph. Sublimation and solution crystallization are investigated as methods for controlled crystal growth to isolate the two polymorphs; however, conditions for controlled growth are limited. In terms of morphology, the addition of the PVP to the suberic acid during particle formation creates more round and smooth particles. This morphology is consistent over time. Particles formed from a solution of 31.25 wt% suberic acid/68.75% PVP are initially amorphous but transition to partially crystalline over time, while particles formed from a solution of 25 wt% suberic acid/75 wt% PVP show no signs of transitioning to crystalline after 29 weeks. Knowledge about these phase transformation kinetics of a compound can be beneficial to the pharmaceutical industry for better understanding and predicting the shelf life of a drug. Partial Least Squares Regression is used as a kinetic model to quantify this phase transformation using standards.
Suberic Acid, Polymorphism, Amorphous Dispersions, Crystallization, Solvent Evaporation
Honors Thesis (Bucknell Access Only)
Bachelor of Science in Chemical Engineering
Ryan C. Snyder
Ditmar, Erin, "Crystal Growth and Phase Transformation Kinetics of Suberic Acid Polymorphs and Amorphous Dispersions formed from Monodisperse Droplet Evaporation" (2018). Honors Theses. 443.