Design And Development Of Fast Dissolving Tablets Of Mefenic Acid Prepared By Spherical Crystallization Technique

Abstract

Mefenamic acid is a Non Steroidal anti- inflammatory drug   belonging to the BCS class II. It has a low oral bioavailability due to poor aqueous solubility and poor dissolution rate. The present study was undertaken to improve the dissolution, absorption, and bioavailability of Mefenamic acid by employing spherical agglomeration followed by the development of fast dissolving tablets (FDTs). Spherical agglomerates were prepared using the quasi-emulsion solvent diffusion technique with N,N-dimethyl formamide, water, and chloroform as the good solvent, poor solvent, and bridging liquid, respectively. Pluronic F-68 was used as carrier in drug-to-carrier ratios of 1:0.5, 1:0.75, and 1:1. The prepared agglomerates were evaluated for practical yield, drug content, solubility, flow properties, particle size, scanning electron microscopy, and in vitro dissolution. Microscopic studies confirmed the formation of spherical agglomerates with improved flowability and significantly enhanced dissolution. Optimized agglomerates were compressed into FDTs using co-processed superdisintegrants containing croscarmellose sodium and crospovidone in ratios of 1:1, 1:2, and 1:3. The formulation containing a 1:3 ratio (F9) exhibited the fastest drug release and was selected for pharmacokinetic evaluation in New Zealand white rabbits using a validated LC-MS/MS method following a crossover design. Compared with the pure drug, the optimized FDT demonstrated significantly higher Cmax (158.46 ± 0.15 vs. 67.56 ± 0.43 ng/mL), shorter Tmax (6.15 ± 0.14 vs. 11.42 ± 0.32 h), higher Ka (7.76 ± 0.01 vs. 2.92 ± 0.01 h⁻¹), and greater AUC₀–∞ (564.9 ± 1.36 vs. 126 ± 1.23 ng·h/mL). These findings indicate that spherical agglomeration combined with optimized FDT formulation markedly enhances the dissolution, oral absorption, and bioavailability of Mefenic acid, thereby providing a faster onset of therapeutic action and improved patient compliance.