Enhancing effect of piperidone derivatives on the percutaneous absorption of indomethacin.
Following our previous demonstration that Azone and 2-n-alkylcyclohexanones enhanced the percutaneous absorption of indomethacin, six 1-n-alkylpiperidones were prepared and examined as potential transdermal absorption enhancers. In vitro skin experiments showed that indomethacin absorption enhancement was related to the lipophilicity of the enhancer, and that 1-n-dodecyl piperidone caused the greatest enhancement. The structure of this piperidone is similar to that of Azone, and both compounds had similar lipophilicity and drug absorption enhancement activity. We suggest that they act in the same way by decreasing diffusional resistance in the stratum corneum, and so modifying the hard barrier of the stratum corneum.
Quan
D Y
DY
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Higuchi
R I
RI
Takayama
K
K
Higashiyama
K
K
Nagai
T
T
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003512:Cyclohexanones / Q000494:pharmacology; D005079:Excipients; D066298:In Vitro Techniques; D007213:Indomethacin / Q000493:pharmacokinetics*; D010880:Piperidines / Q000494:pharmacology*; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013552:Swine
D001381:Azepines; D003512:Cyclohexanones; D005079:Excipients; D010880:Piperidines; C035229:laurocapram; D007213:Indomethacin