The effects of some permeability enhancers on the percutaneous absorption of lidocaine.
Local anesthesia of the intact skin is difficult because of the barrier properties of skin to epicutaneous penetration of local anesthetic drugs. Using local anesthetics with combination of penetration enhancers could overcome this problem. The main objective of this study was to assess the effects of some permeability enhancers on the percutaneous permeation of lidocaine. The effect of polysorbate 80, polysorbate 20, dimethylsulfoxide (DMSO), tert-butyl cyclohexanol (TBCH), and alpha-terpinol in different concentrations and various ratios of lidocaine to enhancers was evaluated. The results showed that polysorbate 80 and polysorbate 20 has no detectable penetration enhancing effects in guinea pig skin mounted to diffusion cells. The same results were obtained to water/oil ratio and the type of oil phase (liquid paraffin vs. castor oil). Addition of DMSO to the previous formulations had a considerable enhancing effect. According to the data, the extent of lidocaine permeation was proportional to the concentration of DMSO in these formulations. The best results belonged to the addition of terpenes but interestingly there wasn't any linear relationship between the concentrations of alpha- terpinol/ or TBCH and the duration of antinociceptive effects of lidocaine. Based on the results of this study the ratio of 1: 4 from alpha- terpinol or TBCH to lidocaine results in a better antinociceptive effect and alpha- terpinol was the best one among of these compounds. This effect was proven with in vivo tail- immersion test to assess the antinociceptive effect of formulations which have shown more penetration.
Mohammadi-Samani
Soliman
S
Pharmaceutical Research Center, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. smsamani@sums.ac.ir
Jamshidzadeh
Akram
A
Montaseri
Hashem
H
Rangbar-Zahedani
Mojgan
M
Kianrad
Roshan
R
D000279:Administration, Cutaneous; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000081005:Cyclohexane Monoterpenes; D003511:Cyclohexanols / Q000494:pharmacology; D053138:Cyclohexenes / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004347:Drug Interactions; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D039821:Monoterpenes / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy; D010539:Permeability / Q000187:drug effects*; D011136:Polysorbates / Q000494:pharmacology; D051381:Rats; D012867:Skin / Q000187:drug effects; D012869:Skin Absorption / Q000187:drug effects*
D000779:Anesthetics, Local; D000081005:Cyclohexane Monoterpenes; D003511:Cyclohexanols; D053138:Cyclohexenes; D039821:Monoterpenes; D011136:Polysorbates; C016775:alpha-terpineol; D008012:Lidocaine; D004121:Dimethyl Sulfoxide