Characterisation of selected active agents regarding pKa values, solubility concentrations and pH profiles by SiriusT3

The aim of this work was to determine pK(a) values and solubility properties of 34 active agents using the SiriusT3 apparatus. The selected drug substances belong to the groups of ACE-inhibitors, beta-blockers, antidiabetics and lipid lowering substances. Experimentally obtained pK(a) and intrinsic solubility values were compared to calculated values (program ACD/ChemSketch) and pK(a) values to published data as well. Solubility-pH profiles were generated to visualise the substance solubility over the gastrointestinal pH range. The relationship between the solubility characteristic of a substance, its bioavailability and categorisation according to the Biopharmaceutics Classification System (BCS) was examined as well. The results showed a good agreement between experimentally obtained, calculated and published pK(a) values. The measured and calculated intrinsic solubility values indicated several major deviations. All solubility-pH profiles showed the expected shape and appearance for acids, bases or zwitterionic substances. The obtained results for the pK(a) and solubility measurements of the examined active agents may help to predict their physicochemical behaviour in vivo, and to understand the bioavailability of the substances according to their BCS categorisation. The easy and reproducible determination of pK(a) and solubility values makes the SiriusT3 apparatus a useful tool in early stages of drug and formulation development. (C) 2015 Elsevier B.V. All rights reserved.