The pKa of the drugs was determined using a SiriusT3 apparatus (Sirius Analytical Instruments Ltd., Forest Row, UK) fitted with an Ag/AgCl double-junction reference electrode and an overhead stirrer at a temperature of 298 K controlled by the Sirius software. UV-metric pKa titrations were carried out in 1.5 mL ion-strength-adjusted water (0.15 M KCl), titrating with either 0.5 M HCl or 0.5 M KOH using nitrogen as purge gas. Titrations were carried out in the pH range of pH 2 to pH 12 with an initial concentration of the drug of 30 mM. All measurements were conducted in triplicate.
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