VBE-1平衡溶解度和表观油水分配系数的测定及其酸碱稳定性的考察

Determination of equilibrium solubility and apparent oil/water partition coefficient of VBE-1 and investigation of its pH stability

目的:测定VBE-1的平衡溶解度和表观油水分配系数,并考察其酸碱稳定性,为药物的制剂设计提供实验依据。方法:采用平衡法和摇瓶法测定VBE-1在不同溶剂中的平衡溶解度以及在正辛醇-水/缓冲溶液中的表观油水分配系数,采用高效液相色谱法测定两者的浓度,并用紫外分光光度法考察VBE-1的酸碱稳定性。结果:VBE-1在PEG-400中的溶解度较大,为(677.47±48.09)g·L^(-1)。在pH4.0~8.0范围内,pH对VBE-1的表观油水分配系数有影响,表现出表观油水分配系数随着pH升高而降低的趋势。pH的升高会引起VBE-1颜色的改变,但此变化为可逆反应。结论:VBE-1具有一定的透过能力,可满足经皮给药的一般要求,其对pH较敏感,实验过程中应避免在强碱条件下操作。

OBJECTIVE To provide a reference for designing formulation of drug by determining equilibrium solubility and apparent oil/water partition coefficient of VBE-1,and investigating its pH stability.METHODS Equilibrium solubility of VBE-1 in different solvents and apparent oil/water partition coefficient in octanol-water/buffer solution systems were determined by equilibrium and shake flask method,respectively.Both parameters were determined by HPLC.The pH stability of VBE-1 was determined by UV spectrophotometer method.RESULTS Solubility of VBE-1in PEG-400 was greater,which was（677.47±48.09）g·L^-1.In pH range of 4.0-8.0,value of apparent oil/water partition coefficient would rise as pH increased.As pH increased,color of VBE-1 would change.However,this was a reversible reaction.CONCLUSION VBE-1 can penetrate stratum corneum to certain extent,which satisfies general requirements for transdermal medication.VBE-1is sensitive to pH,so alkaline conditions should be avoided during experiment.