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Rat abdominal intact skin was treated with fatty acids, fatty amines, or Azone which were dissolved in propylene glycol (PG) and PG appearing in the rat dermis was studied. Analysis was done by Fourier transform infrared/attenuated total reflection (FT-IR/ATR) spectroscopy. The appearance of PG with time seemed to be in three phases when the skin sample was treated with a skin penetration enhancer such as oleic acid: (1) in the first stage, PG penetrated the skin barrier which was not substantially altered, and gradually appeared in the dermis; (2) in the second stage, it rapidly distributed in/throughout the dermis, and this rapid distribution was probably due to the alteration of the dermal structure: the penetration enhancing effect of the enhancer was thought to reach maximal; and (3) in the third stage, PG was saturated in the dermis. The value of T(max alteration), at which the alteration of the dermal structures is completed, showed that the action of both oleic acid and oleylamine were more rapid than other enhancers. Both the value of PG peak area(max) at the third stage which reflects the distribution volume of PG in the dermis and the value of T(sat) at which PG is saturated in the dermis were calculated, and the results suggested that both the distribution volume of PG in the dermis and the time of the saturation varied depending on the enhancer. In conclusion, our present work indicated the importance and necessity of evaluating the rate and extent of appearance of a drug in the dermis to characterize an enhancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavior of Propylene Glycol (PG) in Dermis after Treatment of Rat Intact Skin Surface with Fatty Acids, Fatty Amines or Azone Dissolved in PG.