Transdermal delivery of levosimendan

The aim of this study was to determine if transdermal penetration of levosi mendan, a novel positive inotropic drug, could be enhanced and controlled b y formulation modifications. Penetration of levosimendan across human epide rmis in vitro was determined using abdominal excised skin and diffusion cel ls. Predicted steady-state plasma concentrations of levosimendan were estim ated using permeabilities and pharmacokinetic parameters of levosimendan. F or penetration enhancement we used different pH values, co-solvents, cyclod extrins, surfactants, penetration enhancers, liposomes, and iontophoresis. Sodium lauryl sulfate, ethanol, oleic acid, and soya phosphatidylcholine or their combinations clearly increased levosimendan permeation across the sk in in vitro. Iontophoresis was also an efficient method to increase transde rmal permeation of levosimendan. A hydrophilic co-solvent/penetration enhan cer is needed to achieve better permeability of levosimendan across the ski n. In conclusion, transdermal delivery of levosimendan can be significantly increased by formulation modification. Based on kinetic calculations, ther apeutic plasma concentrations may be achievable transdermally, (C) 2000 Els evier Science B.V. All rights reserved.