title: Experimental determination of the physicochemical properties of lumefantrine.
abstract: BACKGROUND
  The physicochemical properties of lumefantrine, a first line combination medicine for the treatment of uncomplicated falciparum malaria have been determined experimentally rather than theoretically as a guide to understanding its disposition in human.
  
  
  METHODS
  The solubility of lumefantrine in various organic solvents was evaluated by estimating the volume of solvent that completely dissolved 15 mg of the drug. Melting point determination was carried out using a melting point apparatus. Dissociation constant of the drug was determined potentiometrically in 0.1M perchloric acid and partition coefficient was by the method of Leo Hansch, using ratio of the concentration of organic to aqueous phase.
  
  
  RESULTS
  Lumefantrine has a melting point of 128-131 degrees C. Its solubility in selected solvents range from 0.013% in acetonitrile (very slightly soluble) to 7.5% in chloroform and dichloromethane (soluble), and it is practically insoluble (0.002%) in water. The ionization constant (pKa), determined in 0.1 M perchloric acid was found to be 9.35. The Log P lies in the range 2.29-3.52, confirming the lipophilicity of lumefantrine.
  
  
  CONCLUSIONS
  The physicochemical properties of lumefantrine reveal that it is highly lipophilic, weakly basic and readily dissolves in non-polar and/or aprotic organic solvents. While these properties will favour its distribution across cellular membranes, the rate-limiting step will be at the dissolution-absorption stage which will require biopharmaceutical modifications.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.
authors.forename: O A
authors.initials: OA
authors.lastname: Kotila
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.
authors.forename: O O
authors.initials: OO
authors.lastname: Olaniyi
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.
authors.forename: A O
authors.initials: AO
authors.lastname: Adegoke
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.
authors.forename: C P
authors.initials: CP
authors.lastname: Babalola
mesh_terms: D000962:Antimalarials / Q000737:chemistry; D002627:Chemistry, Physical / Q000379:methods*; D002855:Chromatography, Thin Layer; D004983:Ethanolamines / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry*; D006801:Humans; D000078102:Lumefantrine; D012995:Solubility; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D004983:Ethanolamines; D005449:Fluorenes; D000078102:Lumefantrine