Paper-based reaction devices as accelerated platforms in forced degradation studies

Abstract

The stability of pharmaceutical compounds is a central concern in drug development, as degradation can compromise both efficacy and safety. Conventional forced degradation studies, while effective, are often time-consuming and resource-intensive, highlighting the need for accessible and high-throughput alternatives. In this study, we introduce paper-based reaction devices (PRDs) as an innovative platform for accelerating drug degradation experiments. Strips of cellulose paper were employed as reactive microenvironments to investigate the degradation of two model drugs, cyclobenzaprine (CBP) and deflazacort (DFL), under oxidative, acidic, basic, and metal-ion stress conditions. Chromatographic analysis using HPLC-PDA and high-resolution mass spectrometry (HRMS) revealed that the paper interface preserved mechanistic relevance, yielding degradation profiles consistent with solution-based studies while markedly enhancing degradation rates. Mechanistic trends were consistent with the hypothesis that hydroxyl-rich cellulose surfaces promote kinetic amplification through hydrogen-bond-mediated microconfinement. Mass-balance assessments demonstrated reproducibility and validated the reliability of the approach across stress conditions. The PRD approach is proposed as an investigational and preformulation-level tool for early-phase stability assessment, complementing rather than replacing conventional stress testing methods. Its simple, robust, and high-throughput format offers a valuable alternative for rapid stability evaluation during the early stages of drug development and formulation design.