不同溶出介质中辛伐他汀的平衡溶解度和表观油水分配系数测定

Determination of Equilibrium Solubility of Simvastatin in Various Buffers and Its Apparent Oil/Water Partition Coefficient

目的测定辛伐他汀在11种不同溶出介质中的平衡溶解度及在正辛醇-水/缓冲液体系中的表观油水分配系数,为辛伐他汀新剂型的研究开发提供参考。方法采用高效液相色谱(HPLC)法测定辛伐他汀在11种不同溶出介质中的平衡溶解度;采用摇瓶法测定辛伐他汀的表观油水分配系数。结果辛伐他汀在不同pH缓冲液中平衡溶解度无显著性差异,表面活性剂十二烷基硫酸钠(SDS)的加入可使辛伐他汀的平衡溶解度增大约70倍,达到130 mg/L。辛伐他汀在不同pH缓冲液中的表观油水分配系数P约为2.5(lgP=0.39),无显著性差异。结论辛伐他汀水溶性差,属生物药剂学分类系统(BCS)Ⅱ类药物,表面活性剂如SDS能显著增加辛伐他汀在水中的溶解度。辛伐他汀的油水分配系数不受pH的影响。

Objective To determine the equilibrium solubility of simvastatin in 11 kinds of buffers and its partition coefficients for the n-octanol-water/buffer solution system, to provide reference for the research and development of new formulations of simvas- tatin. Methods The HPLC method was established and used to detect the concentration of simvastatin in 11 kinds of buffers ;the parti- tion coefficients for the n-octanol-water/buffer solution systems of simvastatin were determined by shaking flask method. Results Simvastatin show no difference in solution of equilibrium solubility in different pH buffer. Addition of surfactant can increase the equi- librium solubility of simvastatin by 70 fold,reaching 130 mg/L. Simvastatin bad similar oil - water partition coefficient of about 2. 5 in different pH buffer（lg P=0. 39）,with no significant difference. Conclusion Simvastatin is a hydrophobic drug and has poor solubili- ty in water, which belongs to BCS Ⅱ drugs. Surfactant such as SDS canincrease its solubility in water significantly. Oil- water partition coefficient of Simvastatin is not affected by pH.