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Matthew DeFrese

Matthew Defrese PDP19
Predoctoral Fellowship in Pharmaceutics, 2019 University of Kentucky

Investigations of Nanoscale Structural Organization Within the Disordered World of Amorphous Spray Dried Dispersions


Enabling formulations for the enhancement of solubility have become increasingly necessary in modern drug development, as an estimated 90% of new chemical entities are found to be poorly water-soluble. Amorphous solid dispersions (ASDs) have become a proven and powerful strategy to address the insufficient bioavailability of such compounds by greatly enhancing the dissolution rate through disruption of the crystal lattice and delivering the drug in a high energy disordered state, which is generally stabilized by a polymer additive. The success of this approach is evidenced by the striking growth of FDA approvals of such products since the turn of the century. Yet, despite their growing prevalence, many open questions remain with respect to the effects of formulation and processing factors on critical attributes – such as the stability and dissolution 62 of ASDs. For example, spray drying is one of the leading methods of manufacture for these formulations – yet the role of solvent-polymer-drug interactions and their effects on product performance and quality are poorly understood. This project seeks to understand how the role of solvent interactions in spray dried dispersions (SDDs) may dictate product performance by controlling the nanoscale structural organization of these materials in the solution state, which can then be frozen into the solid dispersion due to the rapid drying and solvent removal of the spray drying process. Through the use of advanced characterization techniques, it is expected that a fundamental understanding of drug-polymer interactions on product performance can be developed to aid in the design of robust and reliable medicines of the future.