PAT-BASED MONITORING AND RISK ASSESSMENT FOR SUSTAINED-RELEASE ISOSORBIDE MONONITRATE TABLET FORMULATION FOR CHRONIC STABLE ANGINA

Abstract

Background: Long-term (sustained release) (SR) Isosorbide Mononitrate (ISMN) is an effective and well-tolerated agent that enhances therapeutic effectiveness and increases patient compliance in the management of chronic stable angina. But little work has connected Process “Analytical Technology (PAT) and Quality Risk Management (QRM)” to ensure strong manufacturing and product quality. Methods: The sustained-release isosorbide mononitrate tablets (IM) were formulated using nine formulations (F1- F9) and the wet granulation technique using HPMC K100M and ethyl cellulose. The pre- and post-compression attributes, in vitro drug release, process monitoring by PAT, quality risk evaluation by FMEA and accelerated stability testing as per ICH guidelines were evaluated. Result: Consequently, all the formulations met the quality criteria laid out in the pharmacopoeia and showed good flowability properties, acceptable hardness (5.8–7.4 kg/cm²), friability (0.41–0.74%) and drug content (98.2–99.9%). The most critical process parameters identified by PAT were compression force (RPN = 135), dissolution (RPN = 120), and blend uniformity (RPN = 108) as identified by FMEA. Formulations F6- F8 showed good sustained drug release during 24 hours, while optimized formulation was stable under accelerated storage conditions. Conclusion: The combination of PAT with QRM allowed for efficient process control, minimization of manufacturing inconsistencies, and production of high-quality tablets suitable for treatment of chronic stable angina.