Non-isothermal thermogravimetry as an accelerated tool for the shelf-life prediction of paracetamol formulations

Abstract

In this work, non-isothermal thermogravimetric studies have been carried out on several paracetamol formulations with the aim to predict their shelf-lives under variable storage conditions. Specifically, paracetamol tablets of different brands have been investigated allowing to estimate their pharmaceutical quality by considering the specific drug stability. The proposed protocol is based on the kinetic study of thermogravimetric data by the combination of isoconversional procedures (Friedman and Kissinger-Akahira-Sunose (KAS) methods) and “Master plot” analysis. Accordingly, the kinetics of the paracetamol degradation is totally explored in terms of activation energy, pre-exponential factor and reaction mechanism of the drug decomposition. The obtained insights drive to simulate the decay time functions of paracetamol amount for the several pharmaceutical formulations. Interestingly, these simulations can be easily adapted to variable isothermal conditions providing the shelf-lives of the paracetamol tablets at different temperatures. The kinetic characteristics of the paracetamol degradation as well as the corresponding shelf-life values evidenced that the expiration date of the pharmaceutical products are significantly affected by the composition of the excipients. In conclusion, this work demonstrates that non-isothermal thermogravimetric analysis can be used as efficient and sensitive tool for the prediction of the shelf-lives of paracetamol formulations.