Effect of mixed micelle formulations including terpenes on the transdermal delivery of diclofenac.
The significant inhibitory action of diclofenac formulated in mixed micelles of lecithin with cholate or deoxycholate was observed on the rat hind paw edema induced by carrageenan. In the primary stage, mixed micelle formulation of deoxycholate was more effective compared with that of cholate. However, in the final term, the inhibitory action was similar in both formulations. In a previous study, the flux of diclofenac was greater in the mixed micelle formulation of deoxycholate compared with that of cholate. It was suggested that the permeation rate of diclofenac through skin was proportional to the pharmacological activity. The hind paw edema was quickly inhibited when cyclic monoterpene such as d-limonene or l-menthol was included in the formulations. All the micelle formulations significantly decreased the value of AUC estimated the hind paw thickness-time profile. This suggests that the micelle formulation of cholate in addition to deoxycholate showed significant anti-inflammatory activity to hind paw edema of rats. Incorporation of d-limonene or l-menthol was more effective on the decrease of AUC. A pharmacological study revealed that micelle formulations were able to reduce the skin irritation of chemicals.
Hendradi
Esti
E
Department of Pharmaceutics, Hoshi University, Ebara, Shinagawa-ku, Tokyo, Japan.
Obata
Yasuko
Y
Isowa
Koichi
K
Nagai
Tsuneji
T
Takayama
Kozo
K
D000279:Administration, Cutaneous; D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000737:chemistry; D001682:Biological Availability; D001692:Biological Transport / Q000502:physiology; D002351:Carrageenan / Q000008:administration & dosage / Q000009:adverse effects; D020355:Cholates / Q000008:administration & dosage / Q000493:pharmacokinetics; D053138:Cyclohexenes; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004339:Drug Compounding / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D006614:Hindlimb / Q000187:drug effects; D007267:Injections; D007509:Irritants / Q000009:adverse effects; D000077222:Limonene; D008297:Male; D008610:Menthol / Q000008:administration & dosage / Q000493:pharmacokinetics; D008823:Micelles; D039821:Monoterpenes / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000503:physiopathology; D012869:Skin Absorption / Q000187:drug effects; D013729:Terpenes / Q000008:administration & dosage / Q000493:pharmacokinetics
D001647:Bile Acids and Salts; D020355:Cholates; D053138:Cyclohexenes; D007509:Irritants; D008823:Micelles; D039821:Monoterpenes; D013729:Terpenes; D003840:Deoxycholic Acid; D004008:Diclofenac; D008610:Menthol; D002351:Carrageenan; D000077222:Limonene