Fluorescence spectroscopic investigation of effect of excipients on epidermal barrier and transdermal systems

Excipients are often used in transdermal formulations to overcome the formidable barrier offered by the epidermis in order to achieve the target flux. In this study we describe the use of frequency-domain fluorescence spectroscopy to characterize the effect of two commonly used excipients, propyleneglycol monolaurate (PGML) and oleic acid on stratum corneum and in a silicone-based transdermal delivery system. Fluorescence lifetime and limiting anisotropy for the probe 1,6-diphenyl-1,3,5-hexatriene in isolated human epidermis were measured as a function of formulation treatment. The drop in lifetime ranged from 0.5 to 2.3 ns, indicative of an increased dielectric constant of the lipophilic barrier exposed to all formulations. This increase is due to increased partitioning of the polar excipients from the delivery system into the stratum corneum. The limiting anisotropy showed a drop of 0.1 in the case of the epidermis exposed to oleic acid formulation and not the PGML formulations, indicative of the different modes of action for these two excipients. The fluorescence data suggested fluidization of the silicone matrix by both oleic acid and PGML. The dynamic fluorescence measurements described in this study are a powerful way to screen formulations while gaining valuable mechanistic insight into the mode of flux enhancement in transdermal formulations.