Improvement of transdermal delivery of tetragastrin by lipophilic modification with fatty acids.
The in-vitro permeability of chemically modified tetragastrin with fatty acids through the rat skin was studied. The permeability of these compounds through intact skin and stripped skin of rat was determined with a Franz-type diffusion cell. The permeation of tetragastrin across the intact skin was improved by chemical modification with acetic acid and butyric acid. However, tetragastrin and caproyl-tetragastrin did not permeate across the intact skin up to the end of experiment. The permeation of tetragastrin across the stripped skin was improved by chemical modification, the skin flux of these acyl derivatives being in the order:acetyl > butyroyl > caproyl. The stability of tetragastrin in skin homogenate was also significantly improved by chemical modification with fatty acids. These results suggest that chemical modifications of tetragastrin with fatty acids increases its lipophilicity, which makes it permeable across the stratum corneum. Moreover, the chemical modification reduced the degradation of tetragastrin in the viable skin, resulting an increase in permeation of tetragastrin across the skin.
Setoh
K
K
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Murakami
M
M
Araki
N
N
Fujita
T
T
Yamamoto
A
A
Muranishi
S
S
D000279:Administration, Cutaneous; D000818:Animals; D002463:Cell Membrane Permeability; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004355:Drug Stability; D005069:Evaluation Studies as Topic; D005227:Fatty Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D013758:Tetragastrin / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D005227:Fatty Acids; D013758:Tetragastrin