BEHAVIOR OF PROPYLENE-GLYCOL (PG) IN DERMIS AFTER TREATMENT OF RAT INTACT SKIN SURFACE WITH FATTY-ACIDS, FATTY AMINES OR AZONE DISSOLVED INPG

Rat abdominal intact skin was treated with fatty acids, fatty amines, or Azone which were dissolved in propylene glycol (PG) and PG appearin g in the rat dermis was studied. Analysis was done by Fourier transfor m infrared/attenuated total reflection (FT-IR/ATR) spectroscopy. The a ppearance of PG with time seemed to be in three phases when the skin s ample 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 th e second stage, it rapidly distributed in/throughout the dermis, and t his rapid distribution was probably due to the alteration of the derma l structure: the penetration enhancing effect of the enhancer was thou ght 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 ole ic acid and oleylamine were more rapid than other enhancers. Both the value of PG peak area(max) at the third stage which reflects the distr ibution 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 pr esent work indicated the importance and necessity of evaluating the ra te and extent of appearance of a drug in the dermis to characterize an enhancer. The dermis was also suggested to act as the skin barrier to drug penetration.