Spray Sonocrystallization

Abstract

A spray sonocrystallization (SSC) method is described here for the crystallization of pharmaceutical agents that provides for a tunable crystal size and narrow size distribution in the submicron regime. SSC uses a tapped, flow-through ultrasonic horn (20 kHz) to spray very fine droplets of the solute-containing solution into a continuous flow of antisolvent which induces immediate crystallization with extremely effective mixing. The analgesic 2-carboxyphenyl salicylate (CPS, salsalate) was explored as a test case. The diameter of sonocrystallized CPS could be controlled systematically over the range from 75 to 175 nm. The addition of low concentrations of polyvinylpyrrolidone or sodium dodecyl sulfate to the antisolvent maintained dispersion of the particles without significantly changing particle size or distribution.