Date of Thesis

Spring 2018

Thesis Type

Masters Thesis (Bucknell Access Only)

Degree Type

Master of Science in Chemical Engineering

Major

Chemical Engineering

First Advisor

Dr. Ryan C. Snyder

Keywords

amorphous dispersion, phase transformation kinetics, pharmaceutical, polyvinylpyrrolidone, stability, crystallization

Abstract

Solid particle manufacturing processes in which size and internal structure are controlled are valuable to the development of effective products in the pharmaceutical, cosmetic, and healthcare industries. Within the field of medicine, particle size and structure can be modified to combat the reduction in water solubility, and thus bioavailability, that is often seen with increased complexity of active ingredients. While a crystalline active ingredient’s bioavailability can be improved via structural modification to an amorphous phase, amorphous particles can exhibit lower stability and therefore will recrystallize over time. This work focuses on the thermodynamics and kinetics of phase transformation as well as the quantification of particle phase composition as amorphous to crystalline transition occurs. A vibrating orifice aerosol generator (VOAG) is used to create uniformly sized particles via monodisperse droplet evaporation of a blended (solute and additive in solvent) solution. Blended solutions containing a polyvinylpyrrolidone (PVP) additive and a dicarboxylic acid solute result in varying amounts of particle crystallinity depending on the percentage of PVP in the solution. Once amorphous particles are formed via monodisperse droplet evaporation, phase quantification throughout subsequent recrystallization of dicarboxylic acid is conducted with reasonable accuracy using a Partial-Least-Squares regression technique. Quantification over time allows for a determination of the thermodynamic solubility limit of dicarboxylic acid in PVP, or the composition at which amorphous particles are stable. Phase transformation kinetics and polymer solubility are also assessed using the Avrami crystallization model and the Flory-Huggins solution theory.

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