1 Pharmaceutical Technology and Engineering, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160062, Punjab, India.3 unknown4 Drug Research Academy A, Drug Research Academy, Faculty of Pharmaceutical Sciences, Københavns Universitet5 Drug Research Academy A, Drug Research Academy, Faculty of Pharmaceutical Sciences, Københavns Universitet
The present study deals with the stress degradation studies on amorphous and polymorphic forms of clopidogrel bisulphate. The objective was to characterize the degradation products and postulate mechanism of decomposition of the drug under solid state stress conditions. For that, amorphous form, polymorph I and polymorph II of the drug were exposed to 40 degrees C/75% relative humidity (RH), with and without stressors for 3 months. The samples were analyzed by HPLC, and the relative extent of degradation as well as nature of decomposition was compared among three solid forms. In total, eight degradation products were observed under various stress conditions. The structures of all of them were elucidated using LC-MS/TOF and LC-MS(n) studies. While one matched the known hydrolytic decomposition product of the drug in solution, seven others were new. The postulated degradation pathway and mechanism of decomposition are discussed.
Journal of Pharmaceutical and Biomedical Analysis, 2010, Vol 52, Issue 3, p. 332-44
Chromatography, High Pressure Liquid; Chromatography, Liquid; Computer Simulation; Dosage Forms; Drug Stability; Hot Temperature; Hydrogen-Ion Concentration; Hydrolysis; Light; Mass Spectrometry; Molecular Structure; Oxidation-Reduction; Photolysis; Platelet Aggregation Inhibitors; Reproducibility of Results; Technology, Pharmaceutical; Ticlopidine; Time Factors; X-Ray Diffraction