Controlled liquid antisolvent precipitation using a rapid mixing device

Christian Beck, Sameer V. Dalvi, Rajesh N. Dave

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


Particle formation by the liquid antisolvent (LAS) process involves two steps: mixing of solution-antisolvent streams to generate supersaturation and precipitation (which includes nucleation and growth by coagulation and condensation) of particles. Uniform mixing conditions ensure rapid and uniform supersaturation, making it a precipitation controlled process where the particle size is not further affected by mixing conditions and results in precipitation of ultra-fine particles with narrow particle size distribution (PSD). In this work, we demonstrate that the use of an ultrasonically driven T-shaped mixing device significantly improves mixing of solution and antisolvent streams for precipitation of ultra-fine particles in a continuous operation mode. LAS precipitation of ultra-fine particles of multiple active pharmaceutical ingredients (APIs) such as itraconazole (ITZ), ascorbyl palmitate (ASC), fenofibrate (FNB), griseofulvin (GF), and sulfamethoxazole (SFMZ) in the size range 0.1-30 γm has been carried out from their organic solutions in acetone, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), and ethanol (EtOH). Classical theory of homogeneous nucleation has been used to analyze the result, which suggests that higher nucleation rate results in finer particle size. Interestingly, experimental determination of degree of supersaturation indicates that higher supersaturation does not necessarily result in higher nucleation rate and nucleation rates can be correlated to solvent polarity.

Original languageEnglish (US)
Pages (from-to)5669-5675
Number of pages7
JournalChemical Engineering Science
Issue number21
StatePublished - Nov 1 2010

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Chemical Engineering
  • Industrial and Manufacturing Engineering


  • Antisolvent
  • Drug
  • Micromixing
  • Solvent polarity
  • Stabilizers
  • Ultrasound


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