Determination of Equilibrium Solubility and Apparent Oil/Water Partition Coefficient of 10-methoxycamptothecin

Abstract:

Objective: To determine equilibrium solubility of 10-methoxycamptothecin (10-MCPT) in various media and its partition coefficients for the n-octanol-water/buffer solution systems which would settle fundament for the design and manufacture of a new dosage form. Method: HPLC was used to determine equilibrium solubilities of 10-MCPT. Using shake flask method determination of 10-MCPT in octanol-water/buffer liquid apparent oil-water partition coefficient of system. Result: For the first time 10-MCPT in 10 kinds of solvents and pH buffer solution of solubility were identified, at 25 ℃ when the 10-MCPT equilibrium solubility in water of 1.01 mg·L^-1, the chloroform-methanol 1:1, chloroform and methanol had good solubility in organic solvents. The equilibrium solubility in acid buffer solution was a slight increase in water;in alkaline buffer solution of the equilibrium solubility increases with pH increased;at 25 ℃ 10-MCPT was octanol/water apparent partition coefficient of 29.15 lg (P=1.46), are in octanol/pH 1.0 apparent oil-water partition coefficient is larger in the phosphate buffer [57.29]lg (P=1.76). Conclusion: 10-MCPT poorly soluble in water and slightly soluble in methanol and other organic solvents. Increases of the pH can increase the solubility of 10-MCPT, under the condition of strong acid 10-MCPT have larger oil-water partition coefficient.