Laburpena
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 – 1310 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.
Keywords: Lumefantrine, physicochemical properties, solubility, dissociation constant, partition coefficient
Résumé
Contexte: Les propriétés physico-chimiques d’amodiaquine, une première ligne combinaison médicament pour le traitement des complications le paludisme à falciparum ont été déterminées expérimentalement plutôt que théoriquement comme un guide permettant de comprendre sa disposition en l’homme.
Méthode: La solubilité d’amodiaquine chlorhydrate dans divers solvants organiques a été évaluépar l’estimation du volume de solvant que complètement dissous 15 mg du médicament. Détermination du point de fusion a été effectuée à l’aide d’un appareil à point de fusion. Constante de dissociation de la drogue a été déterminépotentiométrieen 0.1Macide perchlorique et coefficient de partition était par la méthode de LeoHansch, utilisant ratio de la concentration de matières organiques en phase aqueuse.
Résultat: Lumefantrinehasamelting point de 128 - 1310 C. Sa solubilité dans les solvants sélectionnés vont de 0,013 % dans l’acétonitrile (très légèrement soluble) à 7,5 % dans le chloroforme et de dichlorométhane (soluble), et il est pratiquement insoluble ( 0,002 %) dans de l’eau. La constante d’ionisation (pKa), déterminée à 0,1 Mperchloric acide a été trouvé à 9,35 . Le journal Pliesintherange 2,29 - 3,52 , confirmant la lipophilie oflumefantrine.
Conclusion :Les propriétés physico-chimiques d’ amodiaquine indiquent qu’il est fortement lipophiles, faiblement basique et se dissout facilement dans non polaires et/ou aprotique solvatant solvants organiques. Tandis que ces propriétés en faveur de sa répartition à travers les membranes cellulaires, la limitation de débit étape sera à la dissolution-phase d’absorption qui exigera modifications biopharmaceutique.
Correspondence: Professor Chinedum Peace Babalola, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria. E-mail: peacebab2001@yahoo.com and cp.babalola@mail.ui.edu.ng
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