Effect of sucrose fatty acid esters on transdermal permeation of lidocaine and ketoprofen.
The effect of sucrose fatty acid esters on transdermal permeation of lidocaine (LC) and ketoprofen was examined. A drug solution was applied to excised hairless mouse skin pretreated with a sugar ester solution to examine the direct effects of the sugar esters on skin permeability. LC was applied with a pH 6 buffer solution (98.8% ionized), pH 10 buffer solution (99.2% unionized), or propylene glycol, while KP was applied with a pH 6 buffer solution (99.1% ionized), pH 2 buffer solution (98.9% unionized), or propylene glycol. Pretreatment with J-1216 (sucrose laurate, HLB = 16) or J-1205 (sucrose laurate, HLB = 5) significantly increased the permeation of LC from the pH 6 solution and KP from propylene glycol, respectively. The permeability coefficients of the ionized and unionized LC and KP were calculated from the permeability data. The ionized LC and KP permeated even through skin not pretreated with sugar esters, although the permeability coefficients were 24 times and 38 times less than those of the unionized LC and KP, respectively. J-1216 pretreatment increased the permeability of ionized LC from aqueous vehicle 2.7 fold. In the next series of experiments, we formulated 1.5% of J-1205 and J-1216 in various vehicles to examine their effect on the permeation of LC applied on the excised hairless mouse skin with no pretreatment. The results coincided with the results of the pretreatment experiment, and the effect of J-1205 in propylene glycol was more remarkable than that observed in the pretreatment study. When these sugar esters were dissolved in propylene glycol at 1.5%, J-1205 increased significantly the KP permeation rate as well as LC permeation rate, suggesting that the combination of J-1205 and propylene glycol would be a potent vehicle for transdermal formulations.
Okamoto
Hirokazu
H
Faculty of Pharmacy, Meijo University, Nagoya, Japan. okamotoh@ccmfs.meijo-u.ac.jp
Sakai
Takashi
T
Danjo
Kazumi
K
D000279:Administration, Cutaneous; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D004952:Esters; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008012:Lidocaine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D019999:Pharmaceutical Solutions; D014677:Pharmaceutical Vehicles; D012869:Skin Absorption / Q000187:drug effects; D013395:Sucrose / Q000737:chemistry / Q000494:pharmacology*
D000779:Anesthetics, Local; D004952:Esters; D005227:Fatty Acids; D019999:Pharmaceutical Solutions; D014677:Pharmaceutical Vehicles; D013395:Sucrose; D007660:Ketoprofen; D008012:Lidocaine