title: Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants.
abstract: Protolytic equilibria of irbesartan, losartan, and valsartan have been investigated in the presence and absence of differently charged anionic (sodium dodecyl sulfate), cationic (cetyltrimethylammonium bromide), and nonionic (4-octylphenol polyethoxylate and polyoxyethylene (23) lauryl ether) surfactants. Ionization constants were determined by potentiometric titration at a constant ionic strength (0.1 M NaCl) and temperature 25°C. The effect of surfactants was estimated, based on a shift in apparent ionization constants (pKa(app)) determined in micellar solutions against the pKa(w) values in water. The anionic surfactant caused an increase in the pKa(app) values of sartans (up to 1.72 pK units), while the cationic surfactant had an opposite effect and caused a reduction in pKa(app) values (up to -1.44 pK units). These results point out to the fact that the ionizable groups of sartans are involved in electrostatic interactions with the charged surface of the ionic micelles. Shift in the pKa(app) values in the presence of nonionic surfactants (from -0.86 to +1.30) is a consequence of the interactions of drugs with the hydrophilic palisade layer. Significant changes in the distribution profiles of the equilibrium forms (from -44% to +80%) are observed at the biopharmaceutically important pH 4.5 value and can be considered in terms of the potential influence on intestinal absorption and bioavailability.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Grujić
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Popović
authors.affiliation: Department of General and Inorganic Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia. Electronic address: gpopovic@pharmacy.bg.ac.rs.
authors.forename: Gordana
authors.initials: G
authors.lastname: Popović
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Nikolic
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Danica
authors.initials: D
authors.lastname: Agbaba
mesh_terms: D001713:Biphenyl Compounds / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D000077405:Irbesartan; D019808:Losartan / Q000737:chemistry*; D008823:Micelles; D015394:Molecular Structure; D011522:Protons; D012995:Solubility; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*; D013777:Tetrazoles / Q000737:chemistry*; D000068756:Valsartan / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D001713:Biphenyl Compounds; D008823:Micelles; D011522:Protons; D012996:Solutions; D012997:Solvents; D013501:Surface-Active Agents; D013777:Tetrazoles; D014867:Water; D000068756:Valsartan; D000077405:Irbesartan; D019808:Losartan
keywords: acid-base equilibria; biomimetics; drug interaction; micelle; physicochemical properties; surfactants