Controlled antisolvent precipitation of spironolactone nanoparticles by impingement mixing.

Continuous antisolvent precipitation of spironolactone nanoparticles were performed by impingement mixing in this work. In the range of Reynolds numbers (Re) 2108-6325 for the antisolvent water stream and 1771-5313 for the solvent stream, i.e. acetonic drug solution, 302-360 nm drug nanoparticles were achieved. Increasing drug concentration from 25 to 50 and 100 mg/ml led to a significant size increase from 279.0±2.6 to 302.7±4.9 and 446.0±17.3 nm, respectively. "Two-step crystallization" was first observed for spironolactone in the water/acetone system: the drug was precipitated initially as spherical cluster, which rearranged into ordered cuboidal nanocrystals finally. The nanoformulation showed faster dissolution rate in comparison with the raw drug. By combining the impingement mixing and an on-line spray drying, a fully continuous process may be developed for mass-production of dried drug nanoparticles.