Formulation, Development, Optimization, and Evaluation of a Sustained-Release Hydrogel System of Diclofenac Sodium Using Almond and Neem Gums

Abstract

The development of biopolymer-based drug delivery systems has gained significant attention in recent years as an eco-friendly alternative to synthetic polymers. The present study focuses on the formulation, optimization, and evaluation of sustained-release hydrogel microspheres of diclofenac sodium using two natural polysaccharide gums — Neem (Azadirachta indica) and Almond (Terminalia catappa) gums. These natural gums, known for their biocompatibility, biodegradability, and safety, were chemically modified through crosslinking reactions using glutaraldehyde and epichlorohydrin to enhance mechanical integrity and regulate swelling behavior. Hydrogel microspheres were prepared via emulsion polymerization technique and optimized using a 3-factor, 3-level Box–Behnken design (BBD), varying polymer concentration, crosslinker concentration, and drug loading as independent variables. Characterization of the modified gums and microspheres was carried out using FTIR, DSC, XRD, SEM, and Zeta potential analyses. The optimized formulation exhibited particle size of 115.3 µm, entrapment efficiency of 85.2%, and sustained drug release up to 85.3% over 24 hours. The release followed the Korsmeyer–Peppas model (R² = 0.9889, n = 0.62), indicating anomalous (non-Fickian) diffusion — suggesting simultaneous swelling and diffusion-controlled mechanisms. In vivo anti-inflammatory activity in Wistar rats confirmed significant inhibition of carrageenan-induced paw edema, comparable to marketed diclofenac gel formulations, with no observable irritation or adverse effects. Stability studies conducted under ICH conditions demonstrated excellent physical and chemical stability over three months. This study concludes that Neem and Almond gum–based hydrogel microspheres present a promising, green, biocompatible, and sustained-release carrier system for diclofenac sodium, offering potential benefits in pain management and patient compliance.