Date of Thesis

Spring 2019

Thesis Type

Honors Thesis (Bucknell Access Only)

Degree Type

Bachelor of Science in Chemical Engineering

Major

Chemical Engineering

First Advisor

Ryan C. Snyder

Keywords

metastable polymorph, monodisperse droplet evaporation, succinic acid, organic particle phase behavior, organic particle morphology

Abstract

Essential products in the pharmaceutical, food, and healthcare industries are comprised of organic crystalline particles. Manufacturing processes to create organic particles can be controlled to influence morphology and internal structure of organic particles. Within the pharmaceutical industry, particle crystalline composition and morphology affect critical properties including solubility, and thus bioavailability, an essential performance standard for small molecule pharmaceutical products. Solubility of a compound can be positively influenced through crystal modifications including metastable polymorph formation. Incomplete understanding of polymorphic systems can also result in adverse processing results. This thesis focuses on the phase behavior of a polymorphic drug system, specifically in the presence of a polymer additive. A vibrating orifice aerosol generator (VOAG) is used to create uniformly sized particles via monodisperse droplet evaporation of pure component (solute in solvent) and blended (solute and additive in solvent) solutions. Particle samples are analyses for internal crystal structure and morphology via powder X-ray diffraction (pXRD) and scanning electron microscopy (SEM) respectively. Pure component and blended solutions containing polymer excipient result in varied polymorph formation depending on the weight percent of additive in solution. Relative polymorph presence is calculated via pXRD relative peak heights analysis. Quantification of additive effect on metastable polymorph formation allows for insights into nucleation and phase behavior of organic particles including a polymer additive.

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