title: Skin penetration behaviour of sesquiterpene lactones from different Arnica preparations using a validated GC-MSD method.
abstract: Preparations of Arnica montana L. are widely used for the topical treatment of inflammatory diseases. The anti-inflammatory activity is mainly attributed to their sesquiterpene lactones (SLs) from the helenalin and 11alpha,13-dihydrohelenalin type. To study the penetration kinetics of SLs in Arnica preparations, a stripping method with adhesive tape and pig skin as a model was used. For the determination of SLs in the stripped layers of the stratum corneum (SC), a gas chromatography/mass spectrometry method was developed and validated. Thereby the amount of helenalin derivatives was calculated as helenalin isobutyrate, and 11alpha,13-dihydrohelenalin derivatives as 11alpha,13-dihydrohelenalin methacrylate. This GC-MSD method is suitable also to determine low amounts of SLs in Arnica preparations. The penetration behaviour of one gel preparation and two ointment preparations was investigated. The SLs of all preparations show a comparable penetration in and a permeation through the stratum corneum, the uppermost part of the skin. Interestingly, the gel preparation showed a decrease of the penetration rate over 4h, whereas the penetration rate of ointments kept constant over time. Moreover, we could demonstrate that the totally penetrated amount of SLs only depends on the kind of the formulation and of the SLs-content in the formulation but not on the SLs composition or on the used extraction agent.
authors.affiliation: Institute for Pharmaceutical Sciences, Department of Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-University Freiburg, Stefan-Meier-Str. 19, 79104 Freiburg, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Wagner
authors.forename: Irmgard
authors.initials: I
authors.lastname: Merfort
mesh_terms: D000465:Algorithms; D000818:Animals; D018650:Arnica / Q000737:chemistry*; D004355:Drug Stability; D004431:Ear, External / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005782:Gels / Q000032:analysis; D066298:In Vitro Techniques; D007783:Lactones / Q000493:pharmacokinetics; D009824:Ointments / Q000032:analysis; D010936:Plant Extracts / Q000032:analysis; D015203:Reproducibility of Results; D012717:Sesquiterpenes / Q000032:analysis / Q000493:pharmacokinetics*; D045789:Sesquiterpenes, Guaiane; D012869:Skin Absorption; D013552:Swine
chemical_list: D005782:Gels; D007783:Lactones; D009824:Ointments; D010936:Plant Extracts; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C001329:helenalin