Stability of amorphous solid dispersions: Impact of intermolecular drug-polymer interactions

Lindsay Anne Wegiel, Purdue University

Abstract

It is well recognized that delivering a poorly water soluble drug as the amorphous form can be used as a strategy to improve the apparent solubility, thus potentially improving its dissolution rate and bioavailability. However, an amorphous drug will tend to convert to the thermodynamically more stable crystalline form over pharmaceutically relevant timescales. Dispersing the amorphous drug within a suitable carrier, for example a polymer, has been used as a strategy to delay or prevent the crystallization of the drug over the appropriate timescale. The goal of this study is to investigate specific interactions occurring at the molecular level in solid dispersions and to understand how polymers can disrupt molecular self-assembly leading to an amorphous solid in which crystallization is prevented for long time periods. In addition, the use of infrared spectroscopy was evaluated for its ability to help with the rational selection of polymers for solid dispersions. Long term solid state stability against crystallization, along with crystallization kinetics in solution were studied. This project will supply a rational model for designing amorphous formulations that have good solid state stability over a pharmaceutically relevant time scale, and result in the generation of a supersaturated solution upon dissolution that is maintained for a period of time long enough to increase bioavailability.

Degree

Ph.D.

Advisors

Taylor, Purdue University.

Subject Area

Pharmacy sciences

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