Patient in-use, room temperature and accelerated conditions stability evaluation of FDA approved clopidogrel hydrogen sulfate products.

Abstract

The objective of the study was to evaluate patient in-use, room temperature, and accelerated conditions stability of FDA-approved products of clopidogrel hydrogen sulfate (CHS). Four products (A, B, C and D) were stored at 25 °C/60 % RH (room temperature), 30 °C/75 % RH (patient in-use) and 40 °C/75 % RH (accelerated) stability conditions for 12 weeks. The products were characterized for physicochemical properties such as hardness, disintegration, assay, impurities, dissolution, Fourier-transformed infrared (FTIR), near-infrared (NIR), hyperspectral imaging, and X-ray powder diffraction (XRPD). Absorption spectroscopic and diffractometry data indicated polymorphic forms present in the products were not identical. Products A and D contained form Ⅱ, while Products B and C contained form Ⅰ of the drug. No form Ⅰ to form Ⅱ and vice-versa transformation was observed in products after exposure to stability conditions. However, an increase in crystallinity was observed with storage conditions especially at 40 °C/75 % RH. Impurity C and dissolution met pharmacopeial specifications. Dissolved drug varied from 95.2 to 97.1 % in 30 min and impurity C content was 0.04-0.57 %. After storage at various conditions, impurity C content increased insignificantly, still met pharmacopeial specification. However, Products stored at 30 °C/75 % RH (patient in-use) and 40 °C/75 % RH failed to meet dissolution specification of 85 % in 30 min due to an increase in crystallinity. In conclusion, FDA approved products of CHS contained different polymorphic forms, and crystallinity may increase on exposure to patient in-use condition which may impact clinical outcomes.