Forced Degradation Studies: Analytical Methodologies, Applications, and Regulatory Insights – A Systematic Review

Abstract

Forced degradation studies are an essential component of pharmaceutical development, designed to intentionally degrade drug substances and products under conditions more rigorous than standard accelerated conditions. These studies play a pivotal role in validating the specificity of stability-indicating analytical methods. By exposing drug substances to various stress conditions, forced degradation reveals degradation pathways and identifies degradation products, providing critical insights into the molecular stability and chemical behavior of active pharmaceutical ingredients. These insights are instrumental in guiding formulation design, packaging development, and shelf-life determination. However, despite its significance, regulatory guidelines on forced degradation often lack comprehensive instructions, leaving the execution and interpretation of these studies to the discretion of researchers. This review aims to address this gap by providing a systematic examination of forced degradation methodologies, elucidating degradation mechanisms, and summarizing analytical techniques integral to stability-indicating method development. Additionally, it highlights current trends and challenges in forced degradation research, contributing to the advancement of robust and reliable analytical approaches in pharmaceutical science