Mechanism for enhancement effect of lipid disperse system on percutaneous absorption .2.

To further clarify the mechanism involved in the enhancement effect of lipid disperse systems (LDS) on percutaneous absorption, the effect of particle size of LDSs on percutaneous absorption of betahistine (BH), the comparison of the enhancement effect of LDS with the lipid mixtures or the plain LDS, the effect of pretreatment of skin with gel formulation on penetration of LDS-BH and the fluidising effect of LDSs on the stratum corneum (SC) lipids were estimated using Wistar and hairless rats. No major differences in BH absorption were seen between the gel formulations containing LDS with three different particle size (128 +/- 4, 336 +/- 15, 596 +/- 37 nm), prepared using egg phosphatidylcholine (EPC), cholesterol and dicetylphosphate. The percutaneous absorbability of BH from the formulations containing the lipid mixtures or plain LDS did not reach to the extent from EPC-LDS formulation. Following pretreatment with gel formulation containing enhancer (D-limonene or n-octyl-beta-D-thioglucoside), BH absorption significantly decreased at the initial stage after application compared with that from LDS formulation, suggesting the additive enhancement effect of LDS and enhancer on the absorption. The treatment of the SC of hairless rat with LDSs significantly decreased the rotational correlation time (tau(c)) and shifted downwards the slope of curves (tau(c) versus temperature) at temperatures ranging from 25 to 60 degrees C, compared with that of untreated SC. However, the significant differences in the fluidising effect between LDSs with different particle size were not observed. (C) 1997 Elsevier Science B.V.