title: The role of ultrasound in pharmaceutical production: sonocrystallization.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Analytical Chemistry, University of Córdoba, Córdoba, Spain.|Maimónides Institute of Biomedical Research (IMIBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain.
authors.forename: Laura de Los Santos
authors.initials: Lde L
authors.lastname: Castillo-Peinado
authors.affiliation: Department of Analytical Chemistry, University of Córdoba, Córdoba, Spain. qa1lucam@uco.es.|Maimónides Institute of Biomedical Research (IMIBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain. qa1lucam@uco.es.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Luque de Castro
mesh_terms: D003460:Crystallization / Q000379:methods; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D014465:Ultrasonics / Q000379:methods
chemical_list: D004364:Pharmaceutical Preparations
keywords: mechanisms in sonocrystallization; pharmaceuticals; sonocrystallization; sonocrystallization techniques; ultrasound