Dermal permeation of 2-hydroxypropyl acrylate, a model water-miscible compound: effects of concentration, thermodynamic activity and skin hydration.
Frasch-HF; Barbero-AM; Dotson-GS; Bunge-AL
Int J Pharm 2014 Jan; 460(1-2):240-247
The goal of these studies was to measure and interpret the skin permeability characteristics of 2- hydroxypropyl acrylate (HPA) as a model compound that is completely miscible with water. Methods: In vitro permeation from HPA-H2O binary mixtures through human epidermis and silicone membranes was measured. Thermodynamic activities of HPA and H2O in these mixtures were determined. Permeation was also measured through epidermis and silicone from donor solutions with constant HPA activity but different H2O activities. Water uptake into desiccated human stratum corneum (SC) equilibrated with HPA-H2O mixtures was determined. Results Steady-state flux of HPA through silicone was a linear function of HPA activity but not HPA concentration. For epidermis on the other hand, flux increased with HPA activity only for HPA activities .0.35. At constant HPA activity, flux decreased 4.5-fold as water activity decreased from 1 to 0.8. Incubation of SC with HPA-H2O mixtures resulted in substantial changes in SC water content, dependent on the water activity of the mixture and consistent with measured SC water sorption data. Conclusions These experiments provide unequivocal evidence of a substantial increase in epidermal barrier function resulting from SC dehydration. Dehydration-related alterations in the SC appear responsible for the observed flux characteristics.
Skin-exposure; Skin-absorption; Hydroxy-compounds; Acrylates; In-vitro-studies; Thermodynamic-reactions; Water-deprivation; Skin; Chemical-properties; Biological-effects; Physiological-response; Chemical-analysis;
Author Keywords: Skin absorption; Lag time; Stratum corneum; Skin hydration; Acrylic monomers; Thermodynamic activity
H. Frederick Frasch, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
International Journal of Pharmaceutics