Equilibrium solubility and oil-water partition coefficients of novel GPR40 agonist ADD-16 and its sodium salt
Objective To determine the equilibrium solubility and oil-water partition coefficients of ADD-16 and its sodium salt in different solvents,providing a basis for its subsequent in vivo research and formula development.Methods HPLC was used to detect the equilibrium solubility of ADD-16 and its sodium salt in different organic solvents and phosphate buffer solutions with different pH values.The method was also used to detect the oil-water partition coefficients of ADD-16 and its sodium salt in the n-octanol water system.Results The solubility of ADD-16 and its sodium salt in alcohol was high,especially in methanol,with the highest solubility of 8.87 and 333.03 mg·mL-1,respectively.The solubility of ADD-16 and its sodium salt in phosphate buffer increased with pH,and both have the highest solubility(6.63 and 796.86 μg·mL-1,respectively)in a pH 7.4 buffer.The oil-water distribution coefficients of ADD-16 and its sodium salt were 3.29 and-0.45,respectively.Conclusion The solubility of ADD-16 and its sodium salt is influenced by solvent polarity and pH value.After salt formation,the solubility of ADD-16 is obviously improved,and the oil-water distribution coefficient is decreased,indicating better drug formation performance of ADD-16 sodium salts.
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