Quality by design driven systematic development of nanoemulgel of clobetasol-17-propionate for effective treatment of psoriasis

Abstract

Nanoemulgels require two step formulation, the first one being formulation of nanoemulsion followed by the incorporation of nanoemulsion within a gel matrix. The current investigation aimed to formulate a Clobetasol-17-propionate (CP-17) nanoemulgel using QbD approach as anti-psoriatic for plaque type psoriasis. CP-17 was selected as a therapeutic agent to incorporate into the nanoemulsion system and then optimized CP-17 loaded nanoemulsion was incorporated into gelling agent (Carbopol 940) for topical use. Central Composite Design (CCD) was used. The independent factors used were amount of Smix (X1) and amount of gelling agent (X2). The dependent factors were in vitro drug release (Y1), droplet size (Y2) and encapsulation efficiency (Y3). The droplet size, rheological evaluation, PDI, in vitro release, ex vivo permeation and, retention and, in vivo studies were carried out. The nanoemulgel formulated was found to have droplet size within the range of 37.16 ± 21.16 nm. The ex vivo permeability was 44.68 ± 1.21 % and the skin retention was 40.86 ± 0.61 % after 7 h, both of which were greater than the marketed formulation. The CP-17 nanoemulgel showed 1.3-fold higher flux (498.66 ± 14.40 μg/cm2 h) than marketed formulation (383.9 ± 8.59 μg/cm2 h). The apparent permeability coefficient (APC) found to be 1.6 × 10−4 μg/min and 1.27 × 10−4 μg/min, respectively. The in vivo evaluation showed a reduction in PASI scores for erythema, thickness and scaling. The nanoemulgel produces sustained effect of CP-17 on the site of application as localized effect is required. The inflamed stratum corneum will demand hydration as well as targeted therapy, which the CP-17 nanoemulgel successfully provides.