Effect of penetration enhancers on the permeation of the thyrotropin releasing hormone analogue pGlu-3-methyl-His-Pro amide through human epidermis

The effect of the enhancers, cineole and ethanol, on the transdermal penetr ation of the tripeptide, pGlu-3-methyl-His(2)-Pro amide (M-TRH), across hum an epidermal membrane was studied by flow-through diffusion chambers. The a im of the study was to assess whether the biologically active analogue M-TR H displays similar transdermal penetration properties as those demonstrated earlier for the parental peptide, thyrotropin-releasing hormone (TRH) (Mag nusson et al., 1997a Int. J. Pharm. 157, 113-121). Steady-state fluxes with a donor solution of phosphate-buffered saline (PBS) were 0.34 +/- 0.01 mu g/cm(2)h for M-TRH and 0.27 +/- 0.01 mu g/cm(2)h for TRH. Measured over 30 h the total amount penetrated was 8.6 +/- 1.0 and 7.8 +/- 1.7 mu g/cm(2), r espectively. In the presence of 50% ethanol, the flux of the peptides incre ased approximately 3-fold. A donor solution of 3% cineole, in combination w ith 47% ethanol, increased the penetration of M-TRH to 1.60 +/- 0.02 mu g/c m(2)h, compared to 0.92 +/- 0.03 mu g/cm2h for TRH, as reported previously. The corresponding total amount penetrated over 30 h was 41.5 +/- 4.9 and 2 4.9 +/- 1.7 mu g/cm(2), respectively. Our data suggests that enhancers adde d together with the penetrant can theoretically induce changes in the perme ability of the stratum corneum sufficient to promote the transdermal absorp tion of therapeutically relevant amounts of these peptides. This demonstrat es the possibility to deliver classes of compounds that have been viewed as not suitable for transdermal administration. (C) 1999 Elsevier Science B.V . All rights reserved.