title: Influence of the composition of monoacyl phosphatidylcholine based microemulsions on the dermal delivery of flufenamic acid.
abstract: Although microemulsions are one of the most promising dermal carrier systems, their clinical use is limited due to their skin irritation potential. Therefore, microemulsions based on naturally derived monoacyl phosphatidylcholine (MAPL) were developed. The influence of the water, oil and surfactant content on dermal delivery of flufenamic acid was systematically investigated for the first time. A water-rich microemulsion led to significantly higher in vitro skin penetration of flufenamic acid compared to other microemulsions. The superiority of the water-rich microemulsion over a marketed flufenamic acid containing formulation was additionally confirmed. Differences in drug delivery could be explained by alterations of the microemulsions after application. Evaporation of isopropanol led to crystal-like structures of MAPL on the skin surface from the surfactant- or oleic acid-rich microemulsions. In contrast, the formation of this additional barrier was hindered in case of the water-rich microemulsion. The skin penetration of MAPL was additionally analyzed by combined ATR-FTIR and tape stripping experiments, where MAPL itself penetrated only into the initial layers of the stratum corneum, independent of the microemulsion composition. Since a surfactant must penetrate the skin to cause irritation, MAPL can be presumed as a skin-friendly emulsifier with the ability to stabilize pharmaceutically acceptable microemulsions.
authors.affiliation: University of Vienna, Research Platform 'Characterisation of Drug Delivery Systems on Skin and Investigations of Involved Mechanisms', Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Hoppel
authors.affiliation: University of Vienna, Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Life Sciences, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Hanna
authors.initials: H
authors.lastname: Ettl
authors.affiliation: University of Vienna, Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Life Sciences, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Holper
authors.affiliation: University of Vienna, Research Platform 'Characterisation of Drug Delivery Systems on Skin and Investigations of Involved Mechanisms', Althanstraße 14, 1090 Vienna, Austria; University of Vienna, Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Life Sciences, Althanstraße 14, 1090 Vienna, Austria. Electronic address: claudia.valenta@univie.ac.at.
authors.forename: Claudia
authors.initials: C
authors.lastname: Valenta
mesh_terms: D019840:2-Propanol / Q000737:chemistry; D000003:Abattoirs; D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004339:Drug Compounding; D004423:Ear; D004655:Emulsions; D005439:Flufenamic Acid / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000737:chemistry*; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000737:chemistry*; D034421:Sus scrofa; D014835:Volatilization
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003879:Dermatologic Agents; D004655:Emulsions; D008244:Lysophosphatidylcholines; D014677:Pharmaceutical Vehicles; D012997:Solvents; D013501:Surface-Active Agents; D005439:Flufenamic Acid; D019840:2-Propanol
keywords: ATR-FTIR; Flufenamic acid; Microemulsions; Monoacyl phosphatidylcholine; Tape stripping