Adegoke Olajire A, Babalola Chinedum P, Oshitade Oluwaseun S, Famuyiwa Abiola A
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.
Pak J Pharm Sci. 2006 Jan;19(1):1-6.
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.
本研究首次测定了新型抗疟药咯萘啶的理化性质，因为这些参数在文献中尚无全面报道。除了测定咯萘啶及其四磷酸盐在各种溶剂中的溶解度外，还对它们进行了紫外-可见光谱分析。采用Leo-Hansch方法在正辛醇-水混合物中测定了分配系数，并测定了疏水性指数。对四磷酸盐进行了pKa测定。紫外-可见光谱特征表明，碱基和四磷酸盐在190-380nm范围内均有显著的光吸收。在不同溶剂中的溶解度表明，咯萘啶碱基在氯仿中微溶（1.34%），在甲醇中微溶（0.29%），在乙醇中微溶（0.42%），在辛醇和蒸馏水中极微溶。四磷酸盐在水中微溶（1.46%），而在其他溶剂中仅极微溶。在疏水性指数测定中，外推至100%水浓度时，盐的Rm值更高，进一步表明了盐在水中的溶解度更高。log P值测定表明，碱基{log P为0.26±0.02}比盐{log P为-(1.24±0.21)}更具脂溶性。对四磷酸盐进行滴定得到了四个显著的pKa值，外推至碱基时得到的值分别为7.08±0.05、7.39±0.05、9.88±0.05和10.30±0.10。这些结果将为制定合适的剂型提供指导，以提高药物的生物利用度，尤其是口服途径的生物利用度。
