Influence of the polymer on the physicochemical characterization and in vitro cutaneous performance of clobetasol gels

Clobetasol propionate, a topical glucocorticoid, is commonly used to treat inflammatory skin conditions, including atopic dermatitis and psoriasis. However, prolonged use offers risks to patients. This study evaluated the influence of diverse gel-forming polymers (hydroxypropyl methylcellulose, xanthan gum, and chitosan, at 2%) for clobetasol cutaneous delivery (0.05% drug). The formulations were characterized in terms of their appearance, pH, spreadability, rheology, and in vitro drug release. Cutaneous performance, including ex vivo skin permeation and retention (intact and injured skin), in vitro skin adhesion and cytotoxicity, was evaluated. All hydrogels demonstrated favorable characteristics, with a pH of approximately 4. Viscosity did not significantly affect the release rate, which was sustained for 24 h across formulations. Xanthan gum was considered the most promising gel, with higher viscosity and shear-thinning properties, as well as enhanced skin adhesion, without increasing permeation into deeper skin layers, which has been observed for chitosan in intact and injured skin. Hydroxypropyl methylcellulose was also capable of retaining the drug in the upper skin layers; however, its low degree of skin adhesion and low viscosity might reduce its clinical applicability. Importantly, all formulations exhibited superior cytocompatibility compared with the drug solution. Overall, the cutaneous performance of xanthan gum hydrogel is expected to reduce systemic exposure and minimize potential adverse effects.