caa a22 4500 445312084 CHVBK 20180317142633.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s11095-011-0441-6 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0441-6 A Novel Method for the Investigation of Liquid/Liquid Distribution Coefficients and Interface Permeabilities Applied to the Water-Octanol-Drug System [Elektronische Daten] [Paul Stein, Massimiliano di Cagno, Annette Bauer-Brandl] ABSTRACT: Purpose: In this work a new, accurate and convenient technique for the measurement of distribution coefficients and membrane permeabilities based on nuclear magnetic resonance (NMR) is described. Methods: This method is a novel implementation of localized NMR spectroscopy and enables the simultaneous analysis of the drug content in the octanol and in the water phase without separation. For validation of the method, the distribution coefficients at pH = 7.4 of four active pharmaceutical ingredients (APIs), namely ibuprofen, ketoprofen, nadolol, and paracetamol (acetaminophen), were determined using a classical approach. These results were compared to the NMR experiments which are described in this work. Results: For all substances, the respective distribution coefficients found with the two techniques coincided very well. Furthermore, the NMR experiments make it possible to follow the distribution of the drug between the phases as a function of position and time. Conclusion: Our results show that the technique, which is available on any modern NMR spectrometer, is well suited to the measurement of distribution coefficients. The experiments present also new insight into the dynamics of the water-octanol interface itself and permit measurement of the interface permeability. Springer Science+Business Media, LLC, 2011 interface nationallicence logP nationallicence NMR nationallicence octanol-water nationallicence permeability nationallicence Stein Paul Institut for Fysik og Kemi, Syddansk Universitet, Campusvej 55, DK-5230, Odense, Danmark aut di Cagno Massimiliano Institut for Fysik og Kemi, Syddansk Universitet, Campusvej 55, DK-5230, Odense, Danmark aut Bauer-Brandl Annette Institut for Fysik og Kemi, Syddansk Universitet, Campusvej 55, DK-5230, Odense, Danmark aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2140-2146 0724-8741 28:9<2140 2011 28 11095 https://doi.org/10.1007/s11095-011-0441-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0441-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Stein Paul Institut for Fysik og Kemi, Syddansk Universitet, Campusvej 55, DK-5230, Odense, Danmark aut NATIONALLICENCE 700 1- di Cagno Massimiliano Institut for Fysik og Kemi, Syddansk Universitet, Campusvej 55, DK-5230, Odense, Danmark aut NATIONALLICENCE 700 1- Bauer-Brandl Annette Institut for Fysik og Kemi, Syddansk Universitet, Campusvej 55, DK-5230, Odense, Danmark aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2140-2146 0724-8741 28:9<2140 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer