Effect and mechanism of penetration enhancement of organic base and alcohol on glycyrrhetinic acid in vitro.
The aim of the present study was to explore the effects of organic bases and alcohols on the percutaneous absorption of Glycyrrhetinic acid (GA). GA is a metabolite of Glycyrrhizic acid (GL), a major active ingredient of Glycyrrhizae (Gancao) Radices. Skin penetration parameters of GA were obtained via in vitro penetration experiments using intact and stripped mice back skin. Non-aqueous solvent comprising isopropyl myristate (IPM) and alcohols (ethanol, butanol, octanol and dodecanol) loaded with organic base (triethanolamine or triethylamine) were applied to improve the penetration of GA. In order to further confirm the mechanism by which the organic bases enhanced the penetration of GA, conductivity measurement, (1)H NMR spectroscopy and FT-IR analysis were used to observe the formation of ion pair between GA and organic base. The formation of ion pair increased the solubility of GA in the stratum corneum (SC) and its partition into the viable skin, and therefore enhanced the penetration of GA in skin.
Hao
Jiajia
J
School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Sun
Yuming
Y
Wang
Qing
Q
Tong
Xiao
X
Zhang
Hua
H
Zhang
Qing
Q
D000438:Alcohols / Q000737:chemistry / Q000494:pharmacology; D000588:Amines / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology; D005021:Ethylamines / Q000737:chemistry / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008432:Mathematical Computing; D051379:Mice; D008815:Mice, Inbred Strains; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
D000438:Alcohols; D000588:Amines; D004337:Drug Carriers; D004983:Ethanolamines; D005021:Ethylamines; C009546:triethanolamine; D006034:Glycyrrhetinic Acid; C016162:triethylamine