Formulation And Evaluation Of The Fast-Disintegrating Tablet Of Naproxen By Employing Natural Super Disintegrant And Calorie Free Natural Sweetener

Abstract

Objectives: To formulate and optimize fast disintegrating tablets (FDTs) of naproxen, a BCS Class II NSAID, employing Nelumbo nucifera rhizome starch as a novel natural superdisintegrant and Stevia rebaudiana leaf powder as a calorie-free sweetener, to improve dissolution performance and patient compliance in dysphagic, pediatric, and diabetic populations. Methods: Nine formulation batches (SF1–SF9) were prepared by direct compression using a 3² full factorial design, with Nelumbo nucifera rhizome starch (X₁: 10–30 mg) and Crospovidone (X₂: 10–30 mg) as independent variables. Disintegration time (Y₁, minimize) and cumulative drug release at 30 min (Y₂, maximize) were designated as dependent variables. Drug-excipient compatibility was assessed by FTIR and DSC. All batches were evaluated for pre- and post-compression parameters, wetting time, water absorption ratio, and in vitro drug release. The optimized batch was selected based on maximum desirability using Design-Expert® software and subjected to release kinetics modeling, comparative dissolution against Naprosyn® 500, and accelerated stability testing per ICH Q1A(R2). Results: FTIR and DSC confirmed physicochemical compatibility. All batches met pharmacopeial specifications. The optimized formulation SF6 (X₁ = 20 mg, X₂ = 30 mg), selected on the basis of overall desirability score of 0.9117, achieved disintegration time of 74 ± 1.9 s, cumulative drug release of 97.1 ± 2.3% at 30 min, and wetting time of 57.9 ± 1.6 s, significantly outperforming marketed Naprosyn® 500 (81.6 ± 2.1% at 30 min). Drug release followed first-order kinetics with Fickian diffusion (n = 0.29). Stability studies confirmed no significant change in drug content (98.38 ± 0.46%) or disintegration time (77 ± 2.2 s) after three months. Conclusion: The developed naproxen FDT formulation demonstrated superior disintegration and dissolution performance over the conventional marketed product, with excellent stability, offering significant clinical potential for rapid analgesic onset in patient populations with swallowing difficulties. Future in vivo pharmacokinetic evaluation is recommended to confirm bioavailability enhancement and support clinical translation.