Influence of plasticizer type on the structure and drug release characteristics of LM-pectin hydrogels

This study investigated the effects of different plasticizers—castor oil (CO), polyvinylpyrrolidone (PVP), and polyethylene glycol (PEG) with varying molecular weights (MWs)—on the structure and drug-release performance of low-methoxyl pectin (LM-pectin) hydrogels. Theophylline was used as a model drug to evaluate release behavior under physiologically relevant conditions. The incorporation of plasticizers modulated polymer–polymer interactions, swelling behavior, and thermal properties, thereby affecting drug-release kinetics. CO, a hydrophobic triglyceride, created microdomain-induced diffusion pathways; PVP, containing water-affinitive lactam units, facilitated moisture-driven plasticization; and PEG (MW 400/1000/1500), with hydroxyl-terminated chains, established hydrogen bonds with pectin. Structural analyses (FTIR and DSC) revealed that CO disrupted pectin packing, leading to a flexible yet crystalline matrix and enabling the highest cumulative drug release. PVP-based hydrogels exhibited enhanced crystallinity and slower release, whereas PEG formulations showed molecular-weight-dependent behavior. Kinetic calculations confirmed similar patterns, demonstrating non-Fickian transport for PEG400 and PEG1000 (diffusion associated with polymer relaxation) and an additional diffusion-limited profile for PEG1500 attributed to network densification. Among the methods evaluated, CO improved cumulative release, while PEG1500 and PVP promoted extended, lower-rate delivery. The selection of plasticizers must correspond with the design objective: CO for high cumulative release and PEG1500 or PVP for prolonged, diffusion-controlled administration. These results highlight the critical role of the plasticizer type in tailoring hydrogel performance. The LM-pectin formulations developed herein demonstrate potential for application in controlled dermal and mucosal drug-delivery systems.