Effect of penetration modifiers on the dermal and transdermal delivery of drugs and cosmetic active ingredients.
In this study the effect of 2 penetration modifiers, dimethyl isosorbide (DMI) and diethylene glycol monoethyl ether (DGME) on the skin delivery of hydroquinone (HQ), salicylic acid (SA) and octadecenedioic acid (DIOIC) was investigated. Ten percent DMI and DGME were separately formulated into oil-in-water emulsions containing 1.8% HQ, SA and DIOIC, respectively. Skin delivery and the flux across split-thickness human skin of the active ingredients were determined using Franz diffusion cells. An emulsion with 10% water incorporated instead of the water-soluble penetration modifiers served as a control. The study showed that neither 10% DMI nor 10% DGME significantly enhanced the skin permeation of the various lipophilic active ingredients or the uptake into the skin. It was hypothesized that the addition of the penetration modifiers to the emulsions not only enhanced the solubility of the various active ingredients in the skin but also in the formulation, resulting in a reduced thermodynamic activity and hence a weaker driving force for penetration. Therefore, the effect of DMI and DGME on the solubility of the active ingredients in the skin was counteracted by a simultaneous reduction in the thermodynamic activity in the formulation.
Otto
A
A
Unit for Drug Research and Development, North-West University, Potchefstroom Campus, Potchefstroom, South Africa.
Wiechers
J W
JW
Kelly
C L
CL
Hadgraft
J
J
du Plessis
J
J
D003998:Dicarboxylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004058:Diffusion; D004655:Emulsions / Q000737:chemistry; D005026:Ethylene Glycols / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D005260:Female; D006801:Humans; D006873:Hydroquinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007547:Isosorbide / Q000031:analogs & derivatives / Q000737:chemistry; D020156:Salicylic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012869:Skin Absorption; D012995:Solubility; D013816:Thermodynamics
D003998:Dicarboxylic Acids; D004655:Emulsions; D005026:Ethylene Glycols; D005079:Excipients; D006873:Hydroquinones; C528535:octadecenedioic acid; C010111:carbitol; D020156:Salicylic Acid; C040079:2,5-dimethylisosorbide; D007547:Isosorbide; C031927:hydroquinone