Measurement of solid solubility of warfarin in supercritical carbon dioxide and recrystallization study using supercritical antisolvent process

Jheng Ming Ciou, Bo Cheng Wang, Chie Shaan Su, Jun Jen Liu, Ming Thau Sheu

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2 Citations (Scopus)


The solid solubility of an anticoagulant, warfarin, in supercritical CO2 was measured using a semiflow type apparatus at 308.2, 318.2, and 328.2 K from 10 to 18 MPa. The data were correlated using the Chrastil equation and the Méndez-Santiago and Teja equation. The average deviations for calculated and measured solubilities were approximately 10%. Warfarin was recrystallized using a supercritical crystallization process. Because of the extremely low solubility of warfarin in supercritical CO2 (mole fraction on the order of 10-6), the supercritical antisolvent (SAS) process was adopted. The effects of SAS operating parameters were compared and discussed including the operating temperature, operating pressure, solution concentration, spraying nozzle diameter, CO2 flow rate, and solution flow rate. The experimental results proved that low operating temperatures, high solution concentrations, high CO2 flow rates, and low solution concentrations produce small warfarin crystals, whereas the effects of operating pressure and spraying nozzle diameter are negligible. Warfarin crystals with regular habit and mean particle size of 6.6 μm were successfully obtained. Further comparison on solid-state property of warfarin before and after SAS operations was investigated by PXRD, DSC, TGA and FTIR analysis.

Original languageEnglish
JournalAdvanced Powder Technology
Publication statusAccepted/In press - Jan 1 2018



  • Solubility
  • Supercritical antisolvent
  • Warfarin

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Mechanics of Materials

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