Revista de ciencias farmacéuticas y medicamentos emergentes

Method Validation for Equilibrium Solubility and Determination of Temperature Effect on the Ionization Constant and Intrinsic Solubility of Drugs

Kyoowon Baek†, Su Bin Jeon†, Bo Kyung Kim and Nam Sook Kang*

We performed this study to understand the physicochemical properties of drug-like molecules such as pKa and logS0 (logS) values. The first purpose is to compare pKa and logS0 values obtained using a prediction tool and experimental results. The second purpose is to identify the temperature effect of pKa and logS0 for ionizable drugs at 25ºC and 37ºC. PKa and logS0 of ordinary base compounds were significantly changed by increasing the temperature, but acid and amphoteric compounds were not. The third purpose is to validate the shake-flask method using different buffers and stirring and sedimentation times compared with potentiometric experiments. The equilibrium solubility from the shake-flask method had an excellent consistency with the potentiometric method (CheqSol) for crystalline forms. Additionally, measurement of amorphous compounds, which are poorly soluble and metastable in aqueous solutions, was feasible to determine logS0 (and logS) values using the CheqSol technique.