Topical delivery of climbazole to mammalian skin

Abstract

Dandruff is a common condition, affecting up to half the global population of immunocompetent adults at some time during their lives and it has been highly correlated with the over-expression of the fungus Malassezia spp. Climbazole (CBZ) is used as an antifungal and preservative agent in many marketed formulations for the treatment of dandruff. While the efficacy of CBZ in vitro and in vivo has previously been reported, limited information has been published about the uptake and deposition of CBZ in the skin. Hence, our aim was to investigate the skin permeation of CBZ as well as the influence of various solvents on CBZ skin delivery. Four solvents were selected for the permeability studies of CBZ, namely propylene glycol (PG), octyl salicylate (OSal), Transcutol® P (TC) and polyethylene glycol 200 (PEG). The criteria for selection were based on their wide use as excipients in commercial formulations, their potential to act as skin penetration enhancers and their favourable safety profiles. 1% (w/v) solutions of CBZ were applied under infinite and finite dose conditions using Franz type diffusion cells to human and porcine skin. In line with the topical use of CBZ as an antidandruff agent, comparatively low amounts of CBZ penetrated across the skin barrier (<1% of the applied dose of CBZ). Finite dose studies resulted in a higher extraction of CBZ from human skin compared with infinite dose studies (p < 0.05). CBZ was also taken up to a higher extent in porcine skin (>7-fold) compared with human skin (p < 0.05). Nevertheless, no statistical differences were observed in the amounts that permeated across the different membranes. These preliminary results confirm the potential of simple formulations of CBZ to target the outer layers of the epidermis. The PG and OSal formulations appear to be promising vehicles for CBZ in terms of overall skin extraction and penetration. Future work will expand the range of vehicles studied and explore the reasons underlying the retention of CBZ in the outer layers of the skin.

Characterization and topical delivery of phenylethyl resorcinol

“…The lower permeability of human skin compared with porcine skin is in line with findings reported by other researchers . However, the differences between PR permeated though human epidermis and pig skin were not statistically significant for PG and glycerol solutions ( P > 0.05).…”

“…The mass of PG and DMI solutions started to decrease at 67.2 and 43.1 min, respectively. The evaporation of PG was consistent with previous studies . The amounts of DMI, PG and glycerol vehicles remaining at 1440 min were 69.5 ± 2.4, 48.4 ± 3.0 and 124.0 ± 1.6%, respectively.…”

“…This could explain the higher skin retention observed in porcine skin compared to human skin (P < 0.05). The higher retention in pig skin membrane was also consistent with the results reported by others [36]. From the results obtained in this study, the permeability of human and porcine skin clearly is dependent on the molecule of interest.…”

“…The mass of PG and DMI solutions started to decrease at 67.2 and 43.1 min, respectively. The evaporation of PG was consistent with previous studies [36,37]. The amounts…”

Topical delivery of niacinamide: Influence of neat solvents

“…Even though the mechanism by which TC interacts with the skin is not known, its potential to act as a penetration enhancer has been reported for a number of compounds (Lane, 2013). Puglia and Bonina (2008) PG is a hydrophilic solvent that has been used in topical formulations as a solvent for many actives (Lane, 2013;Haque et al, 2017b;Haque et al, 2018;Paz-Alvarez et al, 2018;Hossain et al, 2019;Iliopoulos et al, 2019;Zhang et al, 2019b). In the present work, 5 μL doses of 3 % (w/w) NIA in PG were applied to porcine skin and the percentage permeation after 24 h was 19.2 %.…”