title: A novel method for the investigation of liquid/liquid distribution coefficients and interface permeabilities applied to the water-octanol-drug system.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut for Fysik og Kemi, Syddansk Universitet, Campusvej 55, DK-5230, Odense, Danmark. pcs@ifk.sdu.dk
authors.forename: Paul C
authors.initials: PC
authors.lastname: Stein
authors.forename: Massimiliano
authors.initials: M
authors.lastname: di Cagno
authors.forename: Annette
authors.initials: A
authors.lastname: Bauer-Brandl
mesh_terms: D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008956:Models, Chemical; D000442:Octanols / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D014867:Water / Q000737:chemistry*
chemical_list: D000442:Octanols; D004364:Pharmaceutical Preparations; D014867:Water