ALCOHOL FLUX AND EFFECT ON THE DELIVERY OF THEOPHYLLINE FROM PROPYLENE-GLYCOL

The diffusion of alcohols and the back-diffusion of water through hair less mouse skin after the application of alcohols have been determined using H-1 NMR spectroscopy to quantitate the composition of the donor phases during diffusion cell experiments. After the alcohols were rem oved, a second application of a standard solute/vehicle (theophylline/ propylene glycol-PG) was made. The diffusion of PG and the back-diffus ion of water were determined using H-1 NMR spectroscopy to quantitate the composition of the donor phases while the diffusion of theophyllin e was determined using UV spectroscopy to quantitate theophylline in t he receptor phases. The flux Values for theophylline, PG and water wer e used as a measure of irreversible damage done to the skins by the in itial application. The flux of the alcohols and the back-diffusion of water in the first application period decreased with increasing chain length of the alcohol. On the other hand, the flux of theophylline, PG and water in the second application increased with increasing chain l ength of the alcohol that had been applied initially. The results from the second application appear to be due to greater irreversible damag e caused by the longer chain alcohols. There is a clear difference bet ween the extent of damage caused by the C-1 to C-3 alcohols and that c aused by the C-4 to C-8 alcohols. (C) 1997 Elsevier Science B.V.