Fast Dynamics of Difluprednate in Micelles or Swollen-Micelles Revealed by ¹⁹F Nuclear Magnetic Resonance Spin Relaxation Rates

Knowledge of molecular rotational dynamics is criticalto interpretsolution nuclear magnetic resonance (NMR) spectroscopy. The observationof sharp solute NMR signals in micelles contradicted the surfactantviscosity effects noted in the Stokes-Einstein-Debye(SED) equation. Herein, the F-19 spin relaxation rates ofdifluprednate (DFPN) drug dissolved in polysorbate-80 (PS-80) micellesand castor oil swollen micelles (s-micelle) were measured and adequatelyfit using an isotropic diffusion model based spectral density function.Despite the high viscosity of PS-80 and castor oil, the fitting resultsrevealed fast 4 and 12 ns dynamics of DFPN in both micelle globules.The observation of the fast ns motion in the viscous surfactant/oilmicelle phase demonstrated motion decoupling between solute moleculesinside micelles and the micelle itself in an aqueous solution. Theseobservations support the role of intermolecular interaction in governingthe rotational dynamics of small molecules, versus the viscosity ofthe solvent molecules as defined in the SED equation.