Development and characterization of an innovative two-component film-spray system for topical administration of hydroquinone.

Hydroquinone (HQ) remains the gold-standard topical agent for skin hyperpigmentation disorders, but its clinical use is limited by pronounced physicochemical instability, particularly its high susceptibility to oxidative degradation. To overcome this limitation, an innovative two-component delivery system was developed, combining a polyvinyl alcohol (PVA)/glycerin polymeric film with an HQ solution applied as a spray, designed to minimize the exposure of HQ to oxidative effects. Three film formulations with varying PVA concentrations (1.5- 3%) were screened based on thickness, mass uniformity, and mechanical resistance. The 2.0% PVA formulation was selected and further optimized by reducing the glycerin content to 0.7%, yielding a uniform, mechanically stable film with adequate thickness (0.1800.022 mm), water absorption (108.875.09%), and surface pH (6.510.23) for topical use. The optimized HQ spray (2% HQ, 0.2% sodium metabisulfite, and purified water) delivered a consistent dose of 1.85 mg HQ/cm² per standardized application (five actuations over 4 cm²). Over a 28-day stability study, refrigeration (4ºC) of HQ solution markedly limited HQ oxidation compared with storage at 25ºC (2.2% vs. 7.6% degradation), a trend paralleled by the pH profiles. Upon combination, spray application onto the film produced a slight, favorable decrease in surface pH (6.180.16), and ATR-FTIR analysis confirmed successful HQ incorporation into the polymeric matrix without major chemical alterations, consistent with predominantly physical incorporation and/or hydrogen-bonding interactions. These results support the two-component film-spray system as a promising strategy to overcome the oxidative instability of conventional HQ formulations, offering a novel approach for the topical delivery of oxidation-prone actives.