Minoxidil Skin Delivery from Nanoemulsion Formulations Containing Eucalyptol or Oleic Acid: Enhanced Diffusivity and Follicular Targeting.

Eman Abd,Michael S Roberts,Jeffrey E Grice,Heather A E Benson

doi:10.3390/pharmaceutics10010019

Abstract

In this work, we examined enhanced skin delivery of minoxidil applied in nanoemulsions incorporating skin penetration enhancers. Aliquots of fully characterized oil-in-water nanoemulsions (1 mL), containing minoxidil (2%) and the skin penetration enhancer oleic acid or eucalyptol as oil phases, were applied to full-thickness excised human skin in Franz diffusion cells, while aqueous solutions (1 mL) containing minoxidil were used as controls. Minoxidil in the stratum corneum (SC), hair follicles, deeper skin layers, and flux through the skin over 24 h was determined, as well as minoxidil solubility in the formulations and in the SC. The nanoemulsions significantly enhanced the permeation of minoxidil through skin compared with control solutions. The eucalyptol formulations (NE) promoted minoxidil retention in the SC and deeper skin layers more than did the oleic acid formulations, while the oleic acid formulations (NO) gave the greatest hair follicle penetration. Minoxidil maximum flux enhancement was associated with increases in both minoxidil SC solubility and skin diffusivity in both nanoemulsion systems. The mechanism of enhancement appeared to be driven largely by increased diffusivity, rather than increased partitioning into the stratum corneum, supporting the concept of enhanced fluidity and disruption of stratum corneum lipids.

Highlights

The horny layer on the skin surface, the stratum corneum (SC), forms a significant barrier that limits the absorption of substances that come in contact with it
The greatest flux was seen with formulations containing eucalyptol as the oil phase, all nanoemulsion formulations gave significantly greater fluxes than controls
We showed that the increased solubility in the nanoemulsion formulations correlated directly with increased solubility of minoxidil in the stratum corneum, this was less pronounced when compared with the aqueous ethanol control (1.7- to 3.3-fold)

Summary

Introduction

The horny layer on the skin surface, the stratum corneum (SC), forms a significant barrier that limits the absorption of substances that come in contact with it. Microemulsions and nanoemulsions are commonly used in topical formulations applied to the skin as therapeutic, cosmeceutical, cosmetic, and personal care products [1]. They offer high solubilization of actives and the potential to manage delivery rates to the skin, in elegant products with good sensorial characteristics. Micro- and nanoemulsions are thermodynamically stable, isotropic systems containing water, oil, surfactants, and cosurfactants in specific ratios They typically have droplets in the sub 100 micron range with low polydispersity (

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