author concluded that the speed of vitamin A depended on the vehicle used. It is
possible that viscosity effects played a role in delivery to the PSU.
Estradiol distribution and penetration was penetration of studies in rat skin
after topical application, by high-resolution autoradiography (50). Estradiol in differ-
ent concentrations was applied in vehicles dimethyl sulfoxide (DMSO), ethylene
glycol, and sesame oil in vivo. It was observed that the rate of estradiol localization
in the sebaceous glands was dependent on the vehicle and dose. At the end of two
hours, the rate of deposition of the drug into the sebaceous glands was more with
DMSO as compared to ethylene glycol. The concentration of estradiol is found to
be the highest in the sebaceous glands at the end of two hours, after which it starts
to decrease. It was observed that radioactivity was retained in the sebaceous glands
for 24 hours or longer in low but significant amounts in all vehicles, suggesting
that a drug depot effect may occur within the PSU.
The importance of the appendageal pathway was also observed in the percu-
taneous absorption of 5% pyridostigmine bromide (hydrophilic) through various
vehicles, which was evaluated using normal and appendage-free scar rat skin in
vitro during 72 hours (51). It was found that the drug absorbed was higher from
nerol 8% in ethanol, followed by azone 5% in ethanol–PG (90:10), followed by
DMSO 10% in ethanol. PG 10% in ethanol inhibited pyridostigmine absorption as
compared to the control, which was an ethanolic solution. In all cases, the absorp-
tion through the appendage-free skin was lower than the absorption through
control skin. The percentage of appendageal pathway was calculated by the
formula (1-Scar skin flux/normal skin flux) 100. It was found that in the first
four hours, the appendageal absorption was most for the DMSO solution, followed
by the proplylene glycol in ethanol, followed by ethanol, then azone solution, and
then the nerol solution. At the end of 72 hours, proplylene glycol in ethanol had the
highest percentage of appendageal transport, followed by DMSO, and the others
were not that significant. The authors suggested that the enhancers (Nerol,
azone) affected the structure of the epidermis, whereas the other solvents
(DMSO, ethanol, and PG) were incorporated in the sebum and dragged the drug
into the sebaceous ducts. These experiments were done under occlusion. It was con-
cluded that ethanol, DMSO, and PG in ethanol favored the transfollicular pathway,
but the other vehicles did not. Since ethanol is primarily a lipid solvent, it can solu-
bilize sebum and allow the migration of the active in the sebaceous glands, explain-
ing why it is primarily transfollicular. It was concluded that by using the right
vehicle it was possible to favor the transfollicular pathway and target the drug.
Radiography was used quantitatively by Fabin et al. (39). Two drugs, tetra-
hydrocannabinol (THC) and oleic acid, were evaluated for delivery into hairless
rat skin appendages with different vehicles in vivo. These vehicles included poly-
ethylene glycol 400 (PEG 400), transcutol, and PG:ethanol (7:3). It was found that
after two hours, THC had the highest penetration from transcutol and the lowest
from PEG 400. After two hours, distribution of THC and oleic acid from transcutol
was not very different. At 24 hours, the transcutol system had delivered the
maximum THC in the different skin layers and PEG 400 delivered the lowest. At
24 hours more, THC had been delivered in the different layers of the skin compared
two hours. It appears that there is a time-dependent effect in the distribution and
localization of the drug in the follicle. In the same experiments, when oleic acid
was added as a vehicle to the PG:ethanol system, the penetration of THC after
two hours was much higher with compared to when oleic acid was not added. It
was concluded that the presence of oleic acid in the delivery system applied to
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