Abstract
Reactive impurities, such as hydrogen peroxide in excipients, raise a great concern over the chemical stability of pharmaceutical products. Traditional screening methods of spiking impurities into solid drug-excipient mixtures oversimplify the micro-environment and the physical state of such impurities in real dosage form. This can lead to an inaccurate prediction of the long-term product stability. This study presents the feasibility of using a polyvinylpyrrolidone-hydrogen peroxide complex (PVP-H(2)O(2)) as an oxidative agent for the solid state forced degradation of a selected drug, vortioxetine HBr. The PVP-H(2)O(2) complex was prepared and characterized using FT-IR spectroscopy. The tablet compacts were made using a mixture of solid PVP-H(2)O(2) complex and crystalline vortioxetine HBr powder. The compacts were exposed to 40 °C/75% RH condition in open and closed states for different time intervals. The extent and the type of drug degradation were analysed using LC and LC-MS. The extent of degradation was higher in the samples stored at the open state as compared to the close state. The solution state forced oxidation was conducted to verify the peroxide induced degradation reactions. The results evidence the utility of the proposed solid-state stressor and the method for screening the sensitivity of drugs to the excipient reactive impurities involving peroxides in solid-state.