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

Area of Science:

• Analytical Chemistry
• Materials Science
• Pharmaceutical Sciences

Background:

• Pharmaceutical compound stability is critical for drug efficacy and safety.
• Conventional forced degradation studies are time-consuming and resource-intensive.
• There is a need for faster, high-throughput stability assessment methods.

Purpose of the Study:

• To introduce paper-based reaction devices (PRDs) as a novel platform for accelerated drug degradation.
• To investigate the degradation of model drugs (cyclobenzaprine and deflazacort) using PRDs.
• To evaluate the mechanistic relevance and reproducibility of PRD-based degradation studies.

Main Methods:

• Utilized cellulose paper strips as microenvironments for drug degradation.
• Subjected model drugs to oxidative, acidic, basic, and metal-ion stress conditions on paper.
• Analyzed degradation products using High-Performance Liquid Chromatography with Photodiode Array detection (HPLC-PDA) and High-Resolution Mass Spectrometry (HRMS).

Main Results:

• PRDs significantly enhanced degradation rates compared to solution-based studies.
• Degradation profiles on paper were mechanistically relevant and consistent with solution studies.
• Hydroxyl-rich cellulose surfaces likely promote kinetic amplification via hydrogen-bond-mediated microconfinement.
• Mass-balance assessments confirmed reproducibility and reliability across various stress conditions.

Conclusions:

• PRDs offer a simple, robust, and high-throughput method for early-phase stability assessment.
• This approach complements conventional stress testing for drug development and formulation design.
• PRDs are valuable for rapid stability evaluation during initial drug development stages.