Michael Moore

Defense Date

8-10-2010

Graduation Date

2010

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Pharmaceutics

School

School of Pharmacy

Committee Chair

Peter Wildfong

Committee Member

Carl Anderson

Committee Member

David Engers

Committee Member

Jennifer Aitken

Committee Member

Ira Buckner

Committee Member

James Drennen

Keywords

Aqueous Solubility; Chemometrics; Molecular Descriptors; Pair Distribution Function; Powder X-ray Diffraction; Solid Dispersion

Abstract

The objective of this work was to introduce a novel method for predicting solid dispersion potential enabled by the ability to differentiate phase-separated co-solidified products from amorphous molecular solid dispersions. The central hypothesis states that a combination of materials properties exists that defines the propensity of an active pharmaceutical ingredient to form a binary amorphous molecular solid dispersion with polyvinylpyrrolidone:vinyl acetate copolymer using a melt-quench procedure. Testing this hypothesis required execution of specific aims directed to address issues inherent to characterizing amorphous materials. The work herein is presented with respect to two separate subjects: (1) analytical development and (2) theoretical applications. In the first few chapters, advanced powder X-ray diffraction data processing techniques are explored and adapted to composite pharmaceutical systems. Specific emphasis will be placed ontotal scattering data manipulations and their benefits over traditional practices. The concluding part of this work is devoted to illustrating the use of materials informatics in modeling solid dispersion potential, ultimately afforded by implementing the materials characterization methodologies developed in the initial stages. Molecular descriptors, commonly employed in quantitative structure-property relationship assessment, were tested for correlation to dispersion potential across a library of small molecule organic compounds. The final model accurately predicted dispersion potential for all 12 calibration compounds and three test compounds.

Format

PDF

Language

English

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