Defense Date


Graduation Date

Spring 5-10-2019


One-year Embargo

Submission Type


Degree Name





School of Pharmacy

Committee Chair

Peter L.D. Wildfong

Committee Member

Ira Buckner

Committee Member

Carl Anderson

Committee Member

Kenneth Morris

Committee Member

Tonglei Li


Amorphous Solid Dispersions, R3m, Quantitative Structure-Property Relationships


Poor aqueous solubility of an active pharmaceutical ingredient (API) is a significant hurdle during drug development. Delivering a drug in its amorphous solid-state is a potential method to overcome this issue, since the amorphous form has increased apparent aqueous solubility. However, the amorphous state is only metastable, and is thermodynamically driven to recrystallize. As a result, pure amorphous drugs are seldom used in marketed products. Intimately mixing a drug in its amorphous form with a polymer, known as an amorphous solid dispersion (ASD), has the potential to significantly extend the physical stability of the amorphous form, while maintaining the benefit of increased apparent solubility. However, ASDs remain poorly understood. As a result, ASDs are primarily developed using a trial and error approach, resulting in increased costs and extended time to market. A method for predicting the probability of successful formation of intimate mixtures of drug and polymer without recrystallization (a.k.a. dispersability) has the potential to reduce costs, shorten development time, and advance scientific understanding of ASDs.

The central hypothesis of this work is that there exists a combination of materials properties that correlates with the probability that an ASD will form in PVPva. Since molecular descriptors are mathematical representations of properties of a molecule, it is hypothesized that they can be successfully applied to predict the formation of amorphous solid dispersions. Specifically, the molecular descriptor R3m was investigated as a tool for the prediction of ASD formation. The work presented herein addresses 3 primary aims: (1) investigating the statistical validity of the model by expanding the model to include 2 preparation methods and 2 concentrations, (2) advancing the understanding of the physicochemical meaning of the R3m descriptor to improve the interpretability of the descriptor, and (3) investigating the relationship between R3m and solubility.



Additional Citations

  1. DeBoyace, K., Wildfong, P.L.D., 2018. The Application of Modeling and Prediction to the Formation and Stability of Amorphous Solid Dispersions. J. Pharm. Sci. 107, 57-74.
  2. DeBoyace, K., Zdaniewski, C., Wildfong, P.L.D., 2018. Differential scanning calorimetry isothermal hold times can impact interpretations of drug-polymer dispersability in amorphous solid dispersions. J. Pharm. Biomed. Anal. 150, 43-50.
  3. DeBoyace, K., Buckner, I.S., Gong, Y., Ju, T., Wildfong, P.L.D., 2018. Modeling and Prediction of Drug Dispersability in Polyvinylpyrrolidone-Vinyl Acetate Copolymer Using a Molecular Descriptor. J. Pharm. Sci. 107, 334-343.