Study of pH-dependent drugs solubility in water

Abstract

The solubilities of five sparingly soluble drug-compounds in water have been measured at constant temperatures (298.1K and 310.1K) by the classical saturation shake-flask method. All substances presented in this work are derivatives of anthranilic acid: flufenamic acid, (FLU), mefenamic acid, (MEF), niflumic acid, (NIF), diclofenac sodium, (DIC), and meclofenamic sodium, (MEC). All of them have anti-inflammatory action. Since the aqueous solubility of the ionized drug is significantly higher than the unionized, the experimental conditions that affect equilibrium solubility values such as composition of aqueous buffer have been examined. The Henderson-Hasselbalch (HH) relationship has been used to predict the pH-dependent solubility profiles of chosen drugs at two temperatures. For this purpose the pKa values of the investigated drugs have been determined with Bates-Schwarzenbach spectrophotometric method at temperature 310.1 K. At temperature 298.1K these values were reported earlier. Similar values of pKa were obtained from the solubility measurements.nema