Development of Multivariate Powder X-ray Diffraction Techniques and Total Scattering Analyses to Enable Informatic Calibration of Solid Dispersion Potential

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.

Name thesis:degree_name

PhD

Level thesis:degree_level

Immediate Access

Discipline thesis:degree_discipline

Pharmaceutics

Year dc:date.available

2010

Author dc:creator

• Moore, Michael

Contributors dc:contributor

• Peter Wildfong
• Carl Anderson
• David Engers
• Jennifer Aitken
• Ira Buckner
• James Drennen

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

Language dc:language

English

Repository record dc:identifier

https://dsc.duq.edu/etd/944

OAI identifier oai:identifier

oai:dsc.duq.edu:etd-1960