Production of Pure Drug Nanocrystals and Nano Co-crystals by Confinement Methods

Flavia Fontana, Patricia Isabel Figueiredo, Pei Zhang, Jouni Tapio Hirvonen, Dongfei Liu, Helder Almeida Santos*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

117 Citations (Scopus)


The use of drug nanocrystals in the drug formulation is increasing due to the large number of poorly water-soluble drug compounds synthetized and due to the advantages brought by the nanonization process. The downsizing processes are done using a top-down approach (milling and homogenization currently employed at the industrial level), while the crystallization process is performed by bottom-up techniques (e.g., antisolvent precipitation to the use of supercritical fluids or spray and freeze drying). In addition, the production of nanocrystals in confined environment can be achieved within microfluidics channels. This review analyzes the processes for the preparation of nanocrystals and co-crystals, divided by top-down and bottom-up approaches, together with their combinations. The combination of both strategies merges the favorable features of each process and avoids the disadvantages of single processes. Overall, the applicability of drug nanocrystals is highlighted by the widespread research on the production processes at the engineering, pharmaceutical, and nanotechnology level.
Original languageEnglish
Pages (from-to)3-21
Number of pages19
JournalAdvanced Drug Delivery Reviews
Publication statusPublished - Jun-2018
Externally publishedYes


  • 317 Pharmacy
  • Nanocrystals
  • Co-crystals
  • Drug
  • Top-down
  • Bottom-up
  • Milling
  • Homogenization
  • Microfluidics
  • Supercritical fluids
  • Spray dryer

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