Determination of the physicochemical properties of pyronaridine - a new antimalarial drug.

Abstract

The physicochemical properties of pyronaridine, a new antimalarial drug, have been determined for the first time in this study, since these parameters are comprehensively not available in literature. UV-Vis spectral analysis of both pyronaridine and its tetraphosphate salt were carried out in various solvents, in addition to solubility of the two drugs in these solvents. Partition coefficient was done in n-octanol-water mixture using the Leo-Hansch method as well hydrophobicity index determination. pKa determination was carried out on the tetraphosphate. UV-Vis spectral characteristics showed that both the base and the tetraphosphate salt have significant light absorption in the range 190-380 nm. Solubility in different solvents revealed that pyronaridine base is sparingly soluble in chloroform (1.34%) while it is slightly soluble in methanol (0.29%) and ethanol (0.42%) and very slightly soluble in octanol and distilled water. The tetraphosphate salt was sparingly soluble in water (1.46%) while it is only very slightly soluble in other solvents. The higher aqueous solubility of the salt was further revealed by a greater Rm value on extrapolation to 100% water concentration in hydrophobicity index determination. Log P value determination showed that the base {log P of 0.26+/-0.02} is more liposoluble than the salt {log P of - (1.240.21)}. Four prominent pKa values were obtained for the tetraphosphate titrated which when extrapolated to the base gave values of 7.08+/-0.05, 7.39+/-0.05, 9.88+/-0.05 and 10.30+/-0.10. The results should guide in formulation of appropriate dosage forms to improve bioavailability of the drug especially from oral routes.