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.

Hexamidine diisethionate (HEX D) has been used for its biocidal actions in topical preparations since the 1950s. Recent data also suggest that it plays a beneficial role in skin homeostasis. To date, the extent to which this compound penetrates the epidermis has not been reported nor how its topical delivery may be where there are minor differences in molecular structures. We also believe that they underline the ongoing necessity for fundamental studies on the interaction of topical excipients with the skin.

Objective Dandruff and its more severe related condition, seborrheic dermatitis affects a high proportion of the population at some point in their life. Piroctone olamine, also known as Octopirox® (OPX) is the monoethanolamine salt of piroctone and is an antifungal agent widely used for the management of dandruff. The aim of the present work was to characterize the physicochemical properties of piroctone olamine and to conduct pre‐formulation studies for the development of novel topical formulations of this active. Methods An HPLC method was developed and validated for the analysis of OPX. The melting point was determined using the DSC Q2000 (TA Instruments, USA). The distribution coefficient (logD(O/PBS)) and partition coefficient (log Po/w) was determined in phosphate‐buffered saline (PBS) AND deionized (DI) water using the shake flask method. All experiments were performed at room temperature. The solubility was determined experimentally by adding amount of active to a solvent. The samples were kept at 32° ± 1°C for 48 h in a water bath. The stability of the compound was determined in a range of solvents by preparing solutions of 1 mg mL−1 in the relevant solvents. These solutions were kept and stirred throughout the experiment at 32 ± 1°C, and aliquots were taken at 24, 48 and 96 h. Results The HPLC method was developed successfully; however, samples at the lower end of the calibration curve showed lower degrees of precision and accuracy. Based on experiments with DSC, the melting point was observed at an onset temperature of 132.4°C. The LogD was determined to be 1.84. The compound had the highest solubility in methanol (278.4 mg mL−1) and propylene glycol (PG), with a value of 248.8 mg mL−1. The lowest solubility for OPX was in dimethyl isosorbide (9.9 mg mL−1), Labrafac™ (3.6 mg mL−1) and isostearyl isostearate (0.5 mg mL−1). Over the 4 days, OPX showed stability in ethanol and PG, while a notable decrease in OPX was observed in PBS and DI water at 32 ± 1°C. Conclusion The physicochemical properties of OPX were characterized to find suitable excipients able to target the epidermis for topical delivery. Building on these findings, future work will focus on the development of novel topical formulation of OPX.