The role of ultrasound in pharmaceutical production: sonocrystallization

Objectives The main aim of this review was to develop a critical discussion of the key role ultrasound (US) can play on the production of active pharmaceutical ingredients (APIs) by discussing the versatile effect this type of energy produces. Methods The different crystallization techniques that can be assisted and improved by US are discussed in the light of the available US devices and the effect pursued by application of US energy. Simple and complex analytical methods to monitor API changes are also discussed. Key findings The countless achievements of API US‐assisted production are summarized in a table, and outstanding effects such as narrower particle size distribution; decreased particle size, induction time, metastable zone and supersaturation levels; or a solubility increase are critically discussed. Conclusions The indisputable advantages of sonocrystallization over other ways of API production have been supported on multiple examples, and pending goals in this field (clarify the effect of US frequency on crystallization, know the mechanism of sonocrystallization, determine potential degradation owing to US energy, avoid calculation of the process yield by determining the concentration of the target drug remaining in the solution, etc.) should be achieved.