Date of Thesis

Spring 2022


Many drugs today exhibit low water solubility, a major concern for the pharmaceutical industry as it results in low drug bioavailability. As a result, several techniques have been developed to circumvent this issue. One such method is amorphous solid dispersions (ASDs), explored in this thesis. Amorphous materials are a class of solids that do not exhibit any long-range order. In other words, the molecules are arranged randomly. ASDs typically contain an active pharmaceutical ingredient (API) and an excipient, usually an amorphous polymer. Although ASDs have greater aqueous solubility, they tend to crystallize negating the benefits of the altered structure. The excipient helps to stabilize the structure slowing or preventing crystallization. However, if the API exceeds the solubility limit of the polymer, crystallization will still occur.

This work uses a Vibrating Orifice Aerosol Generator (VOAG) to make uniform particles, eliminating any effects of size. The particles are composed of succinic or adipic acids as the model APIs and poly(vinylpyrrolidone) (PVP) as the polymer excipient. Scanning electron microscopy (SEM) is used to study the morphology and assess the validity of various assumptions, and powder X-ray diffraction (pXRD or XRD) is used to study the internal structure of the particles.

The internal structure of the samples is monitored to measure the amount of crystalline model API over time. Using standards of known crystallinity made in a spray dryer, the amount of crystalline material in the samples is quantified and the thermodynamic solubility limit is calculated. The Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) equation of state (EOS) is then used to model the thermodynamics of the system.


Material Science, Pharmaceuticals, Amorphous Solid Dispersions, Chemical Engineering

Access Type

Honors Thesis (Bucknell Access Only)

Degree Type

Bachelor of Science


Chemical Engineering

Minor, Emphasis, or Concentration

Computer Science

First Advisor

Ryan Snyder

Second Advisor

Timothy Raymond

Third Advisor

Douglas Collins