TRANSDERMAL DELIVERY OF THEOPHYLLINE FROM ALCOHOL VEHICLES

The fluxes of theophylline (Th) through hairless mouse skin from suspe nsions in straight alkyl chain alcohols have been measured (J(i)). The fluxes of theophylline from these first applications was least from m ethanol (C-1), increased by almost 100-fold for fluxes of theophylline from pentanol (C-5); hexanol (C-6), heptanol (C-7) octanol (C-8) and nonanol (C-9), then decreased 10-fold for the flux of theophylline fro m undecanol (C-11). The second application of a standard solute-solven t, theophylline-propylene glycol (Th-PG), was used to assess damage to the skin caused by the first application. The flux from this subseque nt application of Th-PG (J(j)) was least after application of Th-C-1, increased almost 60-fold after application of Th-C-5, then remained re latively constant after application of theophylline in the longer chai n alcohols. The trend in the fluxes of Th-PG in the second application was the same as the trend in the fluxes of Th-PG subsequent to the ap plication of the neat alcohols previously reported. The ratios J(i)/J( j) showed that there were no significant increases in fluxes of theoph ylline from the first application without concomitant increases in flu xes of theophylline from the second application (J(i)/J(j) = 1.3-2.2) except for the application of Th-C-3 where J(i)/J(j) = 7.7. Control ex periments showed that the fluxes of the alcohols from the suspensions and the back-diffusion of water into the donor phases in the first app lication, determined using H-1 NMR spectroscopy, were of the same magn itude and gave the same trend as from the application of the neat alco hols previously reported. (C) 1998 Elsevier Science B.V. All rights re served.