Enhancing effects of medium chain aliphatic alcohols and esters on the permeation of 6-carboxyfluorescein and indomethacin through rat skin.
Medium chain aliphatic alcohols (C8-C12) and methyl or propyl esters of medium chain fatty acids (C8-C12) enhanced the permeation of 6-carboxyfluorescein (6-CF) and indomethacin (IND) through excised rat skin. The enhancing effects of the aliphatic alcohols for 6-CF and IND decreased with the increase in carbon chain length. The dependence on the carbon chain length was different from that exhibited by medium-chain fatty acids previously reported. In the case of fatty acid esters, the enhancing effects were lower than those of aliphatic alcohols and fatty acids. The relationship between the enhancing effects and the total number of carbon atoms in the esters was different for 6-CF and IND. The dependence on the total number of carbon atoms was similar to that in the aliphatic alcohols for 6-CF, and greater effects were observed in the shorter esters. On the other hand, no definite trends were observed for IND. Although the relationships between the structure and skin permeation-enhancing effect of the aliphatic alcohols and fatty acid esters used in this study are not yet fully understood, they are possible candidates as permeation enhancers for hydrophilic and lipophilic drugs. Further experiments, including examination of the location and environment of the lipophilic carbon chain and hydrophilic groups of such enhancers in the stratum corneum, are needed to optimize transdermal delivery systems containing them.
Seki
Toshinobu
T
Department of Pharmaceutics, Hokkaido College of Pharmacy, Otaru, Hokkaido, Japan.
Morimoto
Kazuhiro
K
D000277:Adjuvants, Pharmaceutic / Q000737:chemistry / Q000493:pharmacokinetics*; D000438:Alcohols / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D004952:Esters; D005452:Fluoresceins / Q000737:chemistry / Q000493:pharmacokinetics*; D007213:Indomethacin / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption
D000277:Adjuvants, Pharmaceutic; D000438:Alcohols; D004952:Esters; D005452:Fluoresceins; C024098:6-carboxyfluorescein; D007213:Indomethacin