Intranasal Delivery of Nicotine Via Thermoresponsive Hydrogel Systems: Design, Characterization, and In Vitro Evaluation

Nicotine replacement therapy (NRT) remains a cornerstone strategy in smoking cessation programs, yet conventional nasal sprays are often limited by mucosal irritation and low patient adherence. This study aimed to develop and characterize a novel thermoresponsive hydrogel nasal formulation that combines Kolliphor P 407 and chitosan to enhance mucosal retention, control nicotine release, and improve patient compliance. Nicotine-containing and nicotine-free hydrogels were prepared with varying concentrations of Kolliphor P 407 and a constant chitosan level. Analytical method validation was performed in accordance with ICH Q2 (R1) guidelines. The physicochemical properties of the formulations, including sol-gel transition temperature, pH, FTIR spectrum, viscosity, and homogeneity, as well as in vitro drug release, were assessed. FTIR analysis confirmed the molecular interactions among the formulation components. In vitro drug release studies demonstrated a controlled, biphasic nicotine release from optimized hydrogel formulations (F2 and F8), characterized by favorable pH and viscosity profiles suitable for nasal administration. The findings suggest that the developed thermoresponsive hydrogel system is a promising and patient-friendly alternative for intranasal nicotine delivery in NRT.