Vaibhav Andhale, Someshwar Mankar, Achal Andhale, Rajashree Ghogare, Suhas Siddheshwar
This study aimed to formulate and optimise a roflumilast loaded ultradeformable transethosomal gel for enhanced topical delivery in psoriasis management, addressing limitations of conventional topical preparations through an advanced vesicular drug delivery approach. Ultradeformable transethosomes were prepared by the ethanol injection technique and optimised using a Box-Behnken experimental design. Independent variables selected were Phospholipon 90G (400-500 mg), Poloxamer 188 (1-3% w/v), and ethanol (20-40% v/v). Dependent responses were vesicle size (Y1), entrapment efficiency (Y2), and zeta potential (Y3), targeting size minimisation, maximum drug entrapment, and optimal negative surface charge respectively. The optimised formulation was incorporated into a Sepineo P600 gel matrix and evaluated for physicochemical properties, in vitro drug release, ex vivo skin permeation, accelerated stability, dermal safety, and in vivo antipsoriatic efficacy using an imiquimod-induced psoriasis model in Wistar rats. Optimised formulation F11, comprising Phospholipon 90G (450 mg), Poloxamer 188 (2% w/v), and ethanol (30% v/v), exhibited vesicle size of 101.4 ± 2.9 nm, entrapment efficiency of 74.38 ± 1.2%, and zeta potential of - 30.21 ± 1.3 mV. Transmission electron microscopy confirmed spherical unilamellar vesicles. Transethosomal gel TG1 demonstrated cumulative drug release of 94.78% and skin permeation of 89.67% over 12 h, surpassing conventional gel. In vivo studies revealed significant PASI score reduction (3.50 ± 0.52 on day 7), enhanced inflammatory biomarker suppression, and improved epidermal repair versus pimecrolimus cream (4.50 ± 0.66, p < 0.01). The optimised roflumilast-loaded ultradeformable transethosomal gel demonstrated improved skin penetration, sustained drug release, and superior preclinical antipsoriatic activity. Further clinical studies are warranted to establish long-term safety and therapeutic efficacy.