Injectable Sodium Hyaluronate Hydrogels Modified by Ionic and Nonionic Polymers Loaded with Prednisolone Disodium Phosphate: Molecular Interactions and Intra-Articular Drug Delivery

Degenerative joint disease is a major cause of disability, and although glucocorticosteroids and hyaluronic acid are widely used to reduce inflammation and improve joint mobility, the development of effective delivery systems remains a challenge. This study describes injectable sodium hyaluronate (HA)-based hydrogels modified with synthetic polymers, including polyacrylic acid (PA), ammonium acryloyldimethyltaurate/VP copolymer (AX), a polyvinyl acetate–polyvinylpyrrolidone mixture (PVA–PVP), and polyethylene glycol 4000 (PEG), loaded with prednisolone disodium phosphate (PSP). The aim was to investigate molecular interactions between PSP and HA-based polymer networks and to determine how these interactions influence hydrogel structure, viscosity, and drug release. Viscosity was measured using a Brookfield rotational viscometer, while intermolecular interactions were analyzed by ATR–FTIR and DSC. Drug release was evaluated using a paddle-over-disc apparatus and quantified spectrophotometrically. Release kinetics were analyzed using zero-, first-, and second-order models as well as the Higuchi, Korsmeyer–Peppas, and Peppas–Sahlin equations. PSP incorporation affected the dynamic viscosity of all formulations, and excipient type also significantly influenced hydrogel viscosity. ATR–FTIR and DSC analyses indicated hydrogen bond formation between PSP and the macromolecules of HA, PA, AX, and PEG. The PA-containing formulation formed the most extensive polymer network structure and exhibited the highest viscosity. Drug release followed mainly first-order, Higuchi, and Korsmeyer–Peppas models, while the release exponent n (0.58 ± 0.01–0.60 ± 0.01) indicated anomalous transport. These findings provide molecular insight into drug–polymer interactions in HA-based hydrogels and highlight their potential as injectable systems for intra-articular delivery of PSP.