title: Characterisation of selected active agents regarding pKa values, solubility concentrations and pH profiles by SiriusT3.
abstract: The aim of this work was to determine pKa values and solubility properties of 34active agents using the SiriusT3 apparatus. The selected drug substances belong to the groups of ACE-inhibitors, β-blockers, antidiabetics and lipid lowering substances. Experimentally obtained pKa and intrinsic solubility values were compared to calculated values (program ACD/ChemSketch) and pKa 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 pKa 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 pKa 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 pKa and solubility values makes the SiriusT3 apparatus a useful tool in early stages of drug and formulation development.
authors.affiliation: University of Greifswald, Center of Drug Absorption and Transport, Institute of Pharmacy, 17487 Greifswald, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Schönherr
authors.affiliation: University of Greifswald, Center of Drug Absorption and Transport, Institute of Pharmacy, 17487 Greifswald, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Wollatz
authors.affiliation: University of Greifswald, Center of Drug Absorption and Transport, Institute of Pharmacy, 17487 Greifswald, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Haznar-Garbacz
authors.affiliation: University of Greifswald, Center of Drug Absorption and Transport, Institute of Pharmacy, 17487 Greifswald, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Hanke
authors.affiliation: Sirius Analytical Ltd., Forest Row, East Sussex RH18 5DW, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Box
authors.affiliation: Sirius Analytical Ltd., Forest Row, East Sussex RH18 5DW, UK.
authors.forename: R
authors.initials: R
authors.lastname: Taylor
authors.affiliation: Sirius Analytical Ltd., Forest Row, East Sussex RH18 5DW, UK.
authors.forename: R
authors.initials: R
authors.lastname: Ruiz
authors.affiliation: Novartis Pharma AG, Technical Research & Development, 4056 Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Beato
authors.affiliation: Vivo Drug Delivery GmbH, 8832 Wollerau, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Becker
authors.affiliation: University of Greifswald, Center of Drug Absorption and Transport, Institute of Pharmacy, 17487 Greifswald, Germany. Electronic address: werner.weitschies@uni-greifswald.de.
authors.forename: W
authors.initials: W
authors.lastname: Weitschies
mesh_terms: D001682:Biological Availability; D001702:Biopharmaceutics; D002626:Chemistry, Pharmaceutical; D006863:Hydrogen-Ion Concentration; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000145:classification; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations
keywords: ACE-inhibitors; Antidiabetics; Biopharmaceutical classification system; Intrinsic solubility; Ionisation constant; Lipid lowering substances; Potentiometric titration; Solubility-pH profile; pK(a) measurement; β-Blockers