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P K Hovsepian

Publications and source records attributed to P K Hovsepian.

4 recordsLinked to original sources
PubMed2001

NMR characterization of a novel bile acid sequestrant, DMP 504.

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.

Bile Acids and Salts↗
PubMed2001

Development and validation of a reverse-phase HPLC method for analysis of efavirenz and its related substances in the drug substance and in a capsule formulation.

A stability-indicating high performance liquid chromatographic (HPLC) method was developed for the assay of efavirenz, a non-nucleoside reverse transcriptase inhibitor used in the treatment of AIDS. The HPLC method, which is used to determine potency in efavirenz capsules and related substances in efavirenz drug substance and capsules, was validated per ICH guidelines. This method, which uses a cyano column, is capable of separating efavirenz from its trans-alkene reduction product. This paper will discuss development and validation of this method, which, to the best of our knowledge, is the first known separation of homologs containing double and triple bonds using reverse-phase HPLC.

Alkynes↗
PubMed2001

Development and validation of a cholate binding capacity method for DMP 504, a bile acid sequestrant.

DMP 504, a highly cross-linked insoluble polymer, is a bile acid sequestrant developed by the DuPont Pharmaceuticals Company for serum cholesterol reduction. Since DMP 504 is insoluble, it was necessary to develop unique specific analytical methods to measure and control the quality of different lots of the drug. Since the mechanism of action of DMP 504 is believed to be by sequestration of bile acids, the in-vitro binding capacity of the polymer for cholic acid was chosen as a surrogate of in-vivo performance and used to assess potency of the compound. In this method, individual aliquots of DMP 504 at three different levels were incubated with a cholate solution of known concentration. The residual cholate solution was filtered and analyzed by a reversed-phase HPLC method using refractive index detection. When the bound cholate was plotted versus the mass of DMP 504, the resulting curve was linear. The slope of this curve is the cholate binding capacity of DMP 504. This method has been shown to be precise and robust. Precision of the method was shown to have an RSD of 2.0% with injection precision of 0.4% and stability of cholate solutions up to 73 h. It is also a unique binding capacity method due to its multi-point determination, and it has been shown to be a suitable quality control method for ensuring lot-to-lot consistency of drug substance.

Cholates↗