Eudragit RS100 based microsponges for dermal delivery of clobetasol propionate in psoriasis management

Abstract

Clobetasol propionate (CP), a super potent dihalogenated topical corticosteroid for psoriasis, displays common side effects like allergic contact dermatitis, steroid acne, skin atrophy, hypo-pigmentation and systemic absorption, on topical application. Hence, entrapment of CP in an appropriate carrier system could minimise the aforementioned side effects, while controlling its percutaneous absorption. Therefore, motive behind current work was to fabricate and evaluate CP loaded microsponges (MS). The microsponges were successfully crafted by employing quasi-emulsion solvent diffusion method. For preparation of MS, organic phase comprising CP, Eudragit RS 100 and dichloromethane was added to aqueous phase (polyvinyl alcohol solution), while stirring. During optimization of MS formulations, factors (drug: polymer ratio, aqueous and organic phase volume) affecting the physical properties of microsponges were also investigated. The prepared microsponges were found to possess particle size in the range 12.2 ± 8.2–45.80 ± 12.3 μm, entrapment efficiency: 60.00 ± 0.06 to 96.37 ± 0.04 % and drug release: 60.60 ± 0.13 to 92.82 ± 0.15 %. Additionaly, CP loaded microsponges were evaluated for topography, thermal and photostability. Finally, optimized CPMS were incorporated into Carbopol gel base, which was subsequently evaluated. In vitro release of CPMS was compared with plain CP and release results were fitted into different kinetic models. CPMS formulation followed zero order kinetics indicating release of drug at constant rate, with absence of initial burst release. This delivery system resulted in extended CP release and its maximum therapeutic activity, with minimum toxic effects. In vivo antipsoriatic activity of CPMS gel performed using mouse tail model exhibited significant therapeutic efficacy in comparison to plain CP gel, which was further supported by the histopathological findings.