Investigation and detection of crystallization from amorphous pharmaceutical systems
Abstract
It is well recognized that rendering a poorly soluble drug amorphous can be used as a strategy to improve the apparent solubility, thus potentially improving its dissolution behavior and bioavailability. However, an amorphous drug has a tendency to convert to the thermodynamically more stable crystalline form over pharmaceutically relevant timescales. Dispersing the amorphous drug with a suitable carrier, for example a polymer, has been used as a strategy to delay or prevent the crystallization of the drugs over the appropriate timescale. Understanding the mechanisms by which polymers inhibit the crystallization of amorphous drugs is important in the design of amorphous solid dispersion formulations. The focus of this project is on probing the ability of chemically diverse polymers, added at low concentration, to inhibit crystallization of amorphous drugs. The impact of several potentially important properties, namely the chemistry of the drug and the polymer, polymer molecular weight, polymer concentration and the presence or absence of specific drug-polymer intermolecular interactions, has been evaluated. Additional studies have focused on investigating the effect of particle size on the bulk crystallization rate both in the presence and absence of polymers with the aim of understanding the role of surface area on crystallization kinetics. Finally, an analytical technique based on a non- linear optical process is explored as a possible sensitive and selective alternative for the detection of crystallization from bulk amorphous powders.
Degree
Ph.D.
Advisors
Taylor, Purdue University.
Subject Area
Pharmacy sciences
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