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. METHOD: 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. RESULT: 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. CONCLUSION: 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.
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. METHOD: 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. RESULT: 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. CONCLUSION: 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: Ameya R Kirtane; Christina Karavasili; Aniket Wahane; Dylan Freitas; Katelyn Booz; Dao Thi Hong Le; Tiffany Hua; Stephen Scala; Aaron Lopes; Kaitlyn Hess; Joy Collins; Siddartha Tamang; Keiko Ishida; Johannes L P Kuosmanen; Netra Unni Rajesh; Nhi V Phan; Junwei Li; Annlyse Krogmann; Jochen K Lennerz; Alison Hayward; Robert Langer; Giovanni Traverso Journal: Sci Adv Date: 2022-05-27 Impact factor: 14.957
Authors: Jie Feng; Chester E Markwalter; Chang Tian; Madeleine Armstrong; Robert K Prud'homme Journal: J Transl Med Date: 2019-06-14 Impact factor: 5.531