In vitro transport of sodium diclofenac across rat abdominal skin: effect of selection of oleaginous component and the addition of alcohols to the vehicle.
The in vitro percutaneous transport of sodium diclofenac from various oil vehicles was examined using rat abdominal skin as a model skin membrane. The overall transport of diclofenac through the skin from the oleaginous vehicles was very poor because of a poor solubility of sodium diclofenac in nonpolar oils. To increase the solubility and the permeability of sodium diclofenac, ethanol and n-octanol were added to each oil (designated as the formulated vehicles). The addition of ethanol and n-octanol to the nonpolar vehicles resulted in an extreme increase in drug solubility in each vehicle, with a remarkable increase in the permeation of diclofenac. The effects of oil components in the formulated vehicle on the permeation of diclofenac across the skin were in the following order: squalane greater than or equal to squalene greater than liquid paraffin greater than middle chain triglyceride greater than olive oil greater than castor oil. In order to clarify the reason for the differences in permeation of diclofenac from these formulated vehicles, the release of diclofenac and n-octanol from these vehicles in vitro was studied. The release rates of n-octanol from the formulated vehicles were in the following order: liquid paraffin greater than squalene greater than or equal to squalane greater than middle chain triglyceride greater than or equal to olive oil greater than castor oil. On the other hand, a linear correlation was observed between the initial release rate of diclofenac from the formulated vehicle and the in vitro permeation of diclofenac through the vehicle to the skin.(ABSTRACT TRUNCATED AT 250 WORDS)
Takahashi
K
K
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, Japan.
Tamagawa
S
S
Katagi
T
T
Yoshitomi
H
H
Kamada
A
A
Rytting
J H
JH
Nishihata
T
T
Mizuno
N
N
D000818:Animals; D004008:Diclofenac / Q000493:pharmacokinetics*; D008297:Male; D009828:Oleanolic Acid / Q000493:pharmacokinetics; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility
D014677:Pharmaceutical Vehicles; D004008:Diclofenac; D009828:Oleanolic Acid