Investigation of piroctone olamine delivery to the skin from single, binary and ternary solvent systems

Disruption of the protective stratum corneum barrier increases the skin's vulnerability to microorganisms and facilitates conditions such as dandruff. Dandruff is a disorder of the scalp that causes increased scaling of the SC and is associated with Malassezia fungus. Consequently, many anti-dandruff commercial products use anti-fungal active ingredients such as piroctone olamine also known as Octopirox (OPX). OPX is an active ingredient used in a number of topical preparations for the management of dandruff. The characterization of the physicochemical properties of OPX was previously reported. The aim of the present work was to investigate a range of solvent systems for their effects on OPX interaction with human skin.

The solvents used in this study were propylene glycol (PG), diethylene glycol monoethyl ether or Transcutol® (TC), PG monolaurate (PGML), isopropyl myristate (IPM), caprylic/capric triglyceride or Labrafac™ Lipophile WL 1349 (LAB), PG caprylate or Capryol® 90 (CAP), isostearyl isostearate (ISIS) and Plurol® Oleique CC 497 (PIOI). The single solvent systems evaluated were PG, TC, PGML, IPM, ISIS and CAP. For the binary solvent systems, PG and TC were examined. Ternary solvent systems consisted of: PG, TC and LAB; PG, PGML and LAB; and PG, TC and IPM. The concentration of OPX used was 1% (w/v). Heat-separated human epidermis was used for 24 h permeation experiments performed under finite dose conditions; mass balance studies were also conducted.

For the six single solvents examined no permeation was evident. Skin permeation of OPX was observed for binary and ternary solvent systems. The highest permeation for all PG:TC binary solvent system ratios tested was from the PG:TC (75:25) system. For the ternary solvent systems investigated, highest cumulative permeation of OPX was observed for PG:PGML:LAB (60:30:10). Considering all systems, PG:TC (75:25) delivered the greatest amount of OPX through the skin. Although OPX is deposited in the skin following the application of neat solvents, higher skin retention values were generally observed for binary and ternary systems.

To our knowledge, this is the first study to examine the permeation behaviour of OPX for a range of single, binary and ternary solvent systems.