DMP 504, a potential
bile acid sequestrant for the treatment of
hypercholesterolemia, is a highly insoluble, cross-linked
polymer which does not lend itself to ordinary means of characterization used for
drug substances in the pharmaceutical industry. Therefore, alternative characterization techniques have been sought. As part of an effort into extensive characterization of
DMP 504 drug substance, nuclear magnetic resonance (NMR) was employed to provide insight into details of the
DMP 504 polymer structure. The primary motivation for determining the structure of the
polymer chain is to relate the
DMP 504 structure to its performance properties as a
bile acid sequestrant. Characterization of the
polymer chain and understanding of the structural basis of its properties is essential in optimizing and controlling the manufacture of reproducible
drug substance. NMR has proven a versatile tool for the description of
polymer structure and dynamics because of the wide range of nuclear interactions affecting the NMR signal. This allows the design of experiments to elicit information about specific
polymer interactions or properties. The methods of sample preparation utilized to obtain NMR spectra of the insoluble
polymer, as well as a discussion and comparison of results for the characterization of
DMP 504 obtained using several different NMR techniques will be presented.