The effect of emulsifiers and penetration enhancers in emulsions on dermal and transdermal delivery

Abstract

Emulsions are widely used as the delivery vehicles of active ingredients. The aim of this project was the investigation of the effect of the emulsifier system on dermal and transdermal delivery. Four different actives with various lipophilicities (propagermanium, hydroquinone, salicylic acid and octa-9,10-decene-1,18-dicarboxylic acid) were investigated. For each active, six different emulsions were formulated which varied only in the emulsifier system. Additionally, the effect of the incorporation of two penetration modifiers into the emulsions, dimethyl isosorbide (DMI) and diethylene glycol monoethyl ether (DGME), on dermal and transdermal delivery was investigated. Analytical methods were developed using gas chromatography with mass spectrometric detection for the quantitative determination of hydroquinone, salicylic acid and octadecenedioic acid in human skin samples and transdermal perfusates. These methods were accurate, precise and reliable and allowed the detection of low concentration of the analytes. Skin permeation experiments were performed using Franz type diffusion cells and human abdominal skin that was dermatomed to a thickness of 400 urn. Delivery of the various actives into the stratum corneum, rest skin and receptor (transdermal) was assessed. Partition coefficients, diffusion coefficients, flux and permeability coefficients were determined from the permeation profiles with the aid of a curve fitting procedure. The experiments revealed that the incorporation of the penetration modifiers did not increase the dermal or transdermal delivery. It was hypothesised that the effect of DMI and DGME on the solubility of the active ingredients in the skin was counteracted by a simultaneous increase in solubility in the formulation and therefore reduction of the thermodynamic activity. The permeation experiments including different emulsifier systems demonstrated that emulsifiers, arranging in liquid crystalline structures in the water phase, enhanced skin penetration of the active ingredients except of salicylic acid. Furthermore, the skin penetration of lipophilic active ingredients was superior from the w/o emulsion compared with the conventional o/w emulsion. The differences in skin penetration were a result of different partitioning behaviour of the active ingredients between the skin and formulation.