Formation of flurbiprofen-ethanolamine complexes and their in vitro permeation across rat skin

Purpose: The purpose of this study was to prepare flurbiprofen (Flu) ethanolamine complexes (Flu-EAs) with appropriate physico-
chemical properties, and investigate their transdermal permeability. Methods: Flurbiprofen monoethanolamine (Flu-MEA) and flurbiprofen triethanolamine (Flu-TEA) complexes were prepared and characterized by DSC and FTIR measurements. The in vitro permeation properties of Flu and Flu-EAs through full-thickness rat skin were investigated using side-by-side diffusion cell systems and with various commonly used pharmaceutical plasticizers or penetration enhancers as the solvents to dissolve the drugs. Results: Flu-MEA and Flu-TEA had lower melting temperatures and octanol/water partition coefficients. The transdermal permeability of the salts was obviously higher than Flu in all the plasticizers and enhancers used. The transdermal permeability of Flu and Flu-EAs in plasticizers was in order of DBS > DBP > TEC > PEG400. The mixtures of penetration enhancers containing Azone provided better enhancing ability for both Flu and Flu-EAs. Conclusion: The in vitro transdermal permeability of Flu can be effectively improved through complex-formation of Flu with monoethanolamine or triethanolamine.

Keywords: Flurbiprofen Ethanolamine Transdermal permeation Plasticizer Penetration enhancer