Solid-state investigations of selected pharmaceutical compounds
Abstract
The following thesis uses the complimentary techniques of single crystal X-ray diffraction, $\sp{13}$C solid-state NMR spectroscopy, X-ray powder diffraction, FT-IR spectroscopy and vapor adsorption to investigate the solid-state properties of specific classes of pharmaceuticals. The first four parts of the thesis examine the macrolide class of antibiotics, semisynthetic erythromycins. The crystallographic structures of many important marketed macrolides are reported for the first time. These structures are erythromycin A dihydrate, erythromycin B dihydrate, clarithromycin anhydrate, and dirithromycin anhydrate form II. The hydrogen bonding networks are examined in detail. Questions surrounding the hygroscopic nature of the dihydrate form of erythromycin A are resolved using a combination of solid-state techniques. Solid-state tautomerism of acetohexamide is investigated using the complimentary techniques of X-ray crystallography, solid-state NMR spectroscopy, and FT-IR spectroscopy. The crystal structure of the marketed polymorphic form of acetohexamide is reported and discussed. The nitro of nizatidine and ranitidine have been shown to exist in solution in both trans and cis configurations. The crystallographic structure of the H$\sb2$ antagonist, nizatidine is reported and compared to ranitidine. Nizatidine is shown to exist in the solid-state only in the cis configuration. Methyl group mobility in the nonsteroidal class of anti-inflammatories is examined using solid-state NMR spectroscopy. These studies attempt to correlate the activation energy for motional processes which bring about spin-lattice relaxation of the methyl group $\sp{13}$C nucleus with solid-state properties. The crystal structure of (S)-(+)-ketoprofen is for the first time reported.
Degree
Ph.D.
Advisors
Byrn, Purdue University.
Subject Area
Pharmacology|Analytical chemistry|Chemistry
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