US EPA

1205148 

Journal Article 

INFLUENCE OF COMPOSITION OF L-MENTHOL ETHANOL-WATER TERNARY SOLVENT SYSTEM ON THE TRANSDERMAL DELIVERY OF MORPHINE HYDROCHLORIDE 

Wada, Y; Nakajima, K; Yamazaki, J; Seki, T; Sugibayashi, K; Morimoto, Y 

1993 

Yes 

Biological and Pharmaceutical Bulletin
ISSN: 0918-6158
EISSN: 1347-5215 

16 

6 

600-603 

English 

8364514 

The influence of concentration of each component in l-menthol-ethanol-water ternary solvent system (MEW system) on the skin permeation of morphine hydrochloride (MPH) was investigated in hairless rats. The cumulative amount of MPH permeated through the excised abdominal skin over 8 h (Q-8) was selected as an index of skin permeability. With changing MPH concentration over a wide range from 0.01 to 10% in a MEW system (5% l-menthol and 40% ethanol), the values of Q-8 were proportional to MPH concentration. The concentration was fixed at 1% for the following experiments. For the effect of the concentration of l-menthol at 40% ethanol, the maximum Q-8 was observed at 5% l-menthol, and no greater enhancement of Q-8 was obtained by increasing l-menthol concentration above that. In the ethanol effect at 5% l-menthol, the maximum Q-8 was observed at 45% ethanol. When 2-propanol and methanol, which are more lipophilic and hydrophilic than ethanol, respectively, were used instead of ethanol, the maximum values of Q-8 were observed at 40 and 55%. The maximum values for Q-8 were obtained in the vicinity of the solubility of l-menthol in the MEW system in all cases, suggesting that the skin permeation enhancing effect of the system is dependent on the thermodynamic activity of l-menthol. 

MORPHINE HYDROCHLORIDE; SKIN PERMEATION; PENETRATION ENHANCER; L-MENTHOL ETHANOL WATER TERNARY SOLVENT SYSTEM