DefinePK

Abstract

The present study aimed to develop and optimize sustained-release (SR) matrix tablets of Nimesulide, a poorly water-soluble NSAID, using HPMC K15 as a hydrophilic polymer to enhance dissolution and prolong drug release. A Box-Behnken design was employed to optimize the formulation by varying concentrations of HPMC K15, Avicel, and magnesium stearate, with hardness and cumulative drug release at 12 hours as key response variables. The optimized formulation (F3) exhibited excellent micromeritic properties, achieving 93.08% drug release over 12 hours, following zero-order kinetics (R² > 0.99) with a super case-II transport mechanism, indicating diffusion-controlled release. Solid dispersion techniques using Soluplus significantly improved the solubility of Nimesulide, BCS Class II drug. Compatibility studies (FTIR, SEM) confirmed no drug-polymer interactions, while accelerated stability studies (40°C, 75% RH for 6 months) demonstrated no significant changes in physicochemical properties. The developed SR tablets complied with pharmacopeial standards for hardness, friability, weight variation, and drug content, offering a cost-effective, stable, and patient-compatible alternative to conventional dosage forms. Pharmacokinetic evaluation revealed that the SR formulation (F3) exhibited prolonged Tmax (6.5 hrs), extended half-life (12.5hrs), and higher AUC (825.8ng·hr/mL) compared to immediate-release formulations, ensuring sustained therapeutic levels with reduced dosing frequency. This study highlights the successful application of Quality-by-Design (QbD) principles in formulating a robust SR system for Nimesulide, potentially minimizing adverse effects while improving bioavailability and patient -compatible.