Y. Takeuchi et al., BEHAVIOR OF PROPYLENE-GLYCOL (PG) IN DERMIS AFTER TREATMENT OF RAT INTACT SKIN SURFACE WITH FATTY-ACIDS, FATTY AMINES OR AZONE DISSOLVED INPG, Biological & pharmaceutical bulletin, 18(2), 1995, pp. 304-309
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.