Effect of disorder on the physicochemical behavior of pharmaceutical compounds
Abstract
In the solid form, pharmaceutical compounds can exist in either the ordered or disordered state, which in turn influences its various properties such as solubility, stability, etc. The purpose of this study is to see how different methods can result in the disordered state in a pharmaceutical compound and how this can then influence its performance. Various functions of the disordered materials were studied including compressibility, hygroscopicity, chemical stability and thermodynamic behavior. In the first part of the work, disorder in three systems, glucose, theophylline and ampicillin was introduced by the process of dehydration and various methodologies were used to characterize and study the effects of the dehydration conditions on behavior. The study then involved the preparation of completely amorphous solid by melt quenching of a different molecule, letrozole, which has not been previously characterized. Determination of the molecular mobility and thermodynamics was carried out by thermal analysis and its correlation to any increase in solubility was studied. Finally, in the last part of the study, the disordered form of griseofulvin was prepared by the process of milling. An unusual thermal behavior of the milled disordered form was observed and detailed experiments were performed to determine the reason behind this observation.
Degree
Ph.D.
Advisors
Byrn, Purdue University.
Subject Area
Pharmacy sciences
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