Determination of physicochemical properties of halofantrine.
The physicochemical properties of halofantrine hydrochloride (HF HCl)--a phenanthrene methanol antimalarial, were determined practically in this study since such experimental values are still unknown. The solubility in different solvents were determined and found to be 0.67%w/v in methanol (slightly soluble); 0.4%w/v in both n-octanol and acidified acetonitrile (slightly soluble); 0.09%w/v (very slightly soluble) and less than 0.002%w/v in warm water (50 degrees C) (practically insoluble). Halofantrine hydrochloride was found to be practically insoluble in water (at room temperature), n-hexane and phosphate buffer solution of pH 7.4. The partition coefficient between n-octanol and water gave a log p in the range of 3.20-3.26 (mean 3.20 +/- 0.04) and this was at variance with the log P of 8.5 estimated theoretically in literature. The value also confirms the lipophilicity of HF HCl. The ionisation constant (pKa) determined in partly aqueous solvent (40% methanol) ranged between 8.10 and 8.20 (mean 8.18 +/- 0.05) and confirms the monobasicity of halofantrine. This value also differed from the theoretical estimation of 9.6. The values obtained confirm the often unpredictable and erratic absorption of HF HCl, which bears direct relationship to the physicochemical properties and support the need for better formulations with improved drug delivery potentials.
Babalola
C P
CP
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Nigeria.
Adegoke
A O
AO
Ogunjinmi
M A
MA
Osimosu
M O
MO
D000962:Antimalarials / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006863:Hydrogen-Ion Concentration; D010616:Phenanthrenes / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D000962:Antimalarials; D010616:Phenanthrenes; C023768:halofantrine