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.

The role of ultrasound in pharmaceutical production: sonocrystallization

“…Evaporation-based and cold-based sonocrystallization. The two classical ways to reach saturationevaporation (when the thermostability of the system was appropriate) [61,[70][71][72] or cooling (when the decrease in solubility of the target drug was significant enough) [40][41][42]60,73] have been assisted by US, and the typical crystallization parameters have been improved in all instances. [42,72] Salting-out sonocrystallization.…”

“…No many authors seem to know that US is not of radiant nature; therefore, ‘US irradiation’ is frequently found in the literature on this matter . Less frequent but also found in US‐related publications is the use of wavelength instead of frequency…”

“…The temperature negatively influences sonocrystallization, the significance of the effect largely depending on the influence of this variable on the solubility of the target system . It was also found that US induces the reduction in the particle size only when this energy was applied to the solution at the initial stage of crystallization . According to the crystallization theory, the rate of nucleation is inversely proportional to the temperature .…”

“…No many authors seem to know that US is not of radiant nature; therefore, 'US irradiation' is frequently found in the literature on this matter. [10,17,42,[58][59][60][61] Less frequent but also found in US-related publications is the use of wavelength instead of frequency. [10] Sonocrystallization history Despite Richards and Loomis reported in 1927 the first study on the effects of US on crystallization, [62] the research in this field was delayed owing to inconsistent results and the lack of proper US devices.…”

Recrystallization of phenacetin and sulfathiazole using the sonocrystallization process

“…Li et al investigated the effect of power ultrasound on the reactive crystallization of cloxacillin benzathine [11]. Kim et al designed a spray sonocrystallization process using a flow-through ultrasonic horn for the crystallization of pharmaceutical agents [12]. Khan et al produced the curcumin powders by the melt sonocrystallization and studied its therapeutic potential [13].…”