Fellowship Sean Delaney: Theoretical and Experimental Investigation of Hydrogen-Bonding Interactions in Amorphous Dispersions

Amorphous dispersions are emerging as one of the most commonly used approaches to increase the bioavailability of poorly soluble drugs. The increased interest in amorphous dispersions has led to growth of the experimental methods that can be used to study these formulations. Experimental solid-state nuclear magnetic resonance investigations into the amorphous dispersions have provided greatly detailed information about the solid-state arrangements that make amorphous dispersions a preferable drug delivery method. However, the generality of studying amorphous dispersions will be greatly enhanced by the use of molecular dynamics simulations. The goal of the proposed research will be to correlate the results from molecular dynamics simulations with the experimental data in order to develop improved methods of predicting drug stability in amorphous dispersions. The proposed research goal will be accomplished through three specific aims revolving around the theoretical reproduction of current solid-state nuclear magnetic resonance data on the indomethacin - poly(vinylpyrrolidone) dispersions, and continued work with different polymer and drugs in the solid-state formulations. Preliminary studies indicate that molecular dynamics simulations can accurately reproduce the experimental data producing another viable method for the investigation of amorphous dispersions.