NMR characterization of a novel bile acid sequestrant, DMP 504

DMP 504, a potential bile acid sequestrant for the treatment of hypercholes terolemia. is a highly insoluble, cross-linked polymer which does not lend itself to ordinary means of characterization used for drug substances in th e pharmaceutical industry. Therefore, alternative characterization techniqu es have been sought. As part of an effort into extensive characterization o f 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 sequestr ant. Characterization of the polymer chain and understanding of the structu ral 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 des ign of experiments to elicit information about specific polymer interaction s or properties. The methods of sample preparation utilized to obtain NMR s pectra of the insoluble polymer, as well as a discussion and comparison of results for the characterization of DMP 504 obtained using several differen t NMR techniques will be presented. (C) 2001 Dupont Pharmaceutical Company. Published by Elsevier Science B.V. All rights reserved.