Biol. Pharm. Bull. 30(7) 1350—1353 (2007)

advantages as an alternative dosage form (i) avoiding firstpass metabolism, (ii) easy discontinuation of administration, and (iii) reduced side effects; however, the stratum corneum, which is the outermost layer of skin, provides a primary barrier to transdermal drug delivery. Pentazocine (PTZ), a relatively short-acting narcotic-antagonist analgesic, is used clinically for the relief of cancerrelated or postoperative pain, and PTZ shows an analgesic effect, a third as strong as morphine. As PTZ has a short halflife of 2 to 3 h and undergoes extensive first-pass metabolism in the liver, conventional therapy with tablets or injection may result in unstable plasma concentration of the drug, which results in the induction of unexpected side effects. Long-term delivery of PTZ is thus needed at a controlled rate in the body for chronic pain management. Mandal et al. have reported the percutaneous absorption of PTZ together with isopropyl myristate (IPM) as an enhancer, however, the enhanced skin permeation of PTZ is considered limited when IPM is used alone, and increased concentration of the enhancer would cause skin irritation. It is well known that the combination of various enhancers improved the percutaneous absorption of drugs much greater than either enhancer alone. Regarding opioid analgesics, Morimoto et al. have reported that the percutaneous absorption of morphine hydrochloride was improved with a combination of l-menthol and ethanol. The cumulative amount of morphine permeated through hairless rat skin over 10 h was 5-fold times higher than the sum of those with 40% ethanol alone and l-menthol alone. In the present study, therefore, we tried to improve the percutaneous absorption of PTZ using a combination of various enhancers. The skin permeation of PTZ through hairless mouse skin as a model membrane was determined using Franz diffusion cells and to select an appropriate enhancer for developing a new transdermal system. The flux, lag time and cumulative amount of permeated PTZ were measured as indicators of skin permeation improvement. Moreover, the effects of the structure of enhancers and hydrophiliclipophilic balance (HLB) on permeation rates of PTZ were discussed.