Development and Validation of Stability-Indicating Methods, Structural Elucidation of Degradation Products, and Influence of Excipients in Pharmaceuticals: Applications to Deflazacort and Cetilistat

• Grant number: 24/10851-2
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Airton Goncalves Salles Junior
• Grantee: Airton Goncalves Salles Junior
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The research proposal encompasses two interrelated projects aimed at deepening the understanding of drug stability, specifically Deflazacort and Cetilistat, through advanced analytical methods and degradation studies. In Project 1, the focus is on developing a stability-indicating method to monitor the oxidative degradation of Deflazacort. The work will include the structural elucidation of oxidative degradation products in solution and the isolation of these compounds. In addition, the mechanism of oxidative degradation in solution will be investigated to clarify the factors leading to the formation of specific products. The research will also explore the influence of excipients on the thermal and mechano-oxidative degradation pathways of the finished product. A key objective is to understand how excipients affect drug stability under these conditions, contributing to predictions of shelf life and safety in commercial formulations. In Project 2, a UPLC method will be developed and validated for the analysis of Cetilistat and its degradation products. Studies will be conducted to understand the behavior of Cetilistat in solution under acidic, basic, and oxidative stress, using agents such as H¿O¿, ACVA, and copper (II). The structural elucidation of the degradation products obtained in solution will be performed to provide detailed characterization of these species. Moreover, the behavior of Cetilistat will be evaluated in the presence of excipients under thermal, photolytic, and mechano-oxidative stress in the solid phase, aiming to identify potential interactions that may impair stability. Finally, kinetic studies will be carried out to determine relevant parameters, such as the degradation rate constant, shelf life, and half-life of the drug, offering a comprehensive understanding of its stability under various stress conditions. (AU)