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 results in collapsed particles whereas low solubility results in irregular particles. Interplay between the vapor pressure of the solvents and the polymer solubility in the medium made possible to prepare particles with more complicated structures such as shriveled and blistery structures. The particle morphology as detected by SEM did not change when 10 wt.% of ketoprofen was added to the precursor solution.
Raula, J., Eerikäinen, H., & Kauppinen, E. I. (2004). Influence of the solvent composition on the aerosol synthesis of pharmaceutical polymer nanoparticles. International Journal of Pharmaceutics, 284(1-2), 13-21. https://doi.org/10.1016/j.ijpharm.2004.07.003