【精选】Influence of the solvent composition on the aerosol synthesis.pdfVIP

International Journal of Pharmaceutics 284 (2004) 13–21 Influence of the solvent composition on the aerosol synthesis of pharmaceutical polymer nanoparticles a ¨ a,1 a,b,∗ Janne Raula , Hannele Eerikainen , Esko I. Kauppinen a Center for New Materials, Helsinki University of Technology, P.O. Box 1602, FIN-02044 VTT, Finland b Aerosol Technology Group, VTT Processes, P.O. Box 1602, Espoo FIN-02044 VTT, Finland Received 30 October 2003; received in revised form 25 June 2004; accepted 6 July 2004 Abstract Spherical, Eudragit L100 polymer nanoparticles with and without a ketoprofen drug were prepared by a novel aerosol flow reactor method. In this method, the polymer solution is sprayed to form nanosized droplets followed by the evaporation of a solvent. A purpose of the work was to explore the effect of solvent, solvent mixture, and co-solute (ketoprofen) on the formation of polymer particle, and particularly on particle morphology. The solvents used, i.e. ethanol, THF, toluene, and water, were selected according to their vapor pressure and dissolution capability for the polymer. At the polymer concentration range from 0.2 to 1.5 g/l of the starting solution, the geometric number mean diameters (GMD) of the particles increased from 75 to 130 nm and from 65 to 100 nm from the solutions of ethanol and THF, respectively. Particle morphology was observed by a scanning electron microscope (SEM). Particles changed from collapsed to irregular via spherical shape in the course of the decreasing solubility of the polymer in the medium. This is critically dependent on the solvent evaporation rate as well as the solute solubility, i.e. fast evaporative removal of solvent