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-H2O2) as an oxidative agent for the solid state forced degradation of a selected drug, vortioxetine HBr. The PVP-H2O2 complex was prepared and characterized using FT-IR spectroscopy. The tablet compacts were made using a mixture of solid PVP-H2O2 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.
Highlights
Pharmaceutical excipients are known to contain trace impurities, such as reactive oxygen species and formaldehyde, often referred to as reactive impurities [1,2]
The Vortioxetine hydrobromide (VOR) was used as a model compound as the susceptibility of VOR to hydrogen peroxide is well documented in a solid state
Methyl group attached to phenyl ring is a site for hydroxylation forming major oxidative degradation products
Summary
Pharmaceutical excipients are known to contain trace impurities, such as reactive oxygen species (as hydrogen peroxides and/or organic hydro peroxides) and formaldehyde, often referred to as reactive impurities [1,2]. The risk of oxidative drug degradation is identified by conducting the forced degradation studies in solution using reagents such as 2,2-azobisisobutyronitrile (AIBN), 4,4-azobis-4-cyanovaleric acid (ACVA), 2,2 -azobis(2-amidinopropane) dihydrochloride (AAPH), and liquid hydrogen peroxide (H2O2) stressors [4,5]. The validity of such approaches for the accurate prediction of instability in solid state products is often limited [6,7]. Some oxidative methods have been reported for the stress studies [8,9], which barely represent the actual solid-state environment in the presence of the relevant excipient
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
