title: Assessment of the percutaneous penetration of indomethacin from soybean oil microemulsion: effects of the HLB value of mixed surfactants.
abstract: The objective of this study was to evaluate the influence of the ratios or the hydrophile-lipophile balance (HLB) values of Cremophor EL and Span 80 on the phase behavior of the O/W microemulsions and the percutaneous absorption and penetration of indomethacin microemulsions. The existence of microemulsion regions is investigated in quaternary systems composed of soybean oil/Cremophor EL and Span 80 (mixed surfactants)/diethylene glycol monoethyl ether (cosurfactant)/water by constructing pseudo-ternary phase diagrams at various Cremophor EL/Span 80 ratios. In addition, five microemulsion formulations with various mixed surfactants HLB values were evaluated by in vitro penetration experiments using mouse skin and Franz diffusion cells. The flux and amount of indomethacin penetration from 5 microemulsion formulations were significantly different from the control, and the enhance ratios ranged from 2.38 to 4.68 and 2.11 to 4.23, respectively. The HLB value of mixed surfactants in the formulations was a principal factor in determining the percutaneous penetration of the drug. The flux and amount of drug penetration increased gradually with increasing content of the lipophilic surfactant Span 80 and skin retention was highest for mixed surfactants with a HLB value of 7.6. Therefore, it is suggested that the presence of mixed surfactants was beneficial in the formation of O/W microemulsions and enhanced percutaneous penetration of indomethacin.
authors.affiliation: Tianjin Key Laboratory of Modern drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, PR China. cliangmei@gmail.com
authors.forename: Liangmei
authors.initials: L
authors.lastname: Chen
authors.forename: Fengping
authors.initials: F
authors.lastname: Tan
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004655:Emulsions; D005079:Excipients; D005990:Glycerol / Q000031:analogs & derivatives; D006601:Hexoses; D066298:In Vitro Techniques; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D012869:Skin Absorption; D013024:Soybean Oil / Q000737:chemistry*; D013501:Surface-Active Agents
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D005079:Excipients; D006601:Hexoses; D013501:Surface-Active Agents; C018665:sorbitan monooleate; C000515:cremophor EL; D013024:Soybean Oil; D005990:Glycerol; D007213:Indomethacin