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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Warfarin
Carbon Dioxide
Carbon dioxide
Solubility
Flow rate
Spraying
Nozzles
Crystals
Crystallization
Particle size
Anticoagulants
Temperature

Keywords

  • Solubility
  • Supercritical antisolvent
  • Warfarin

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Mechanics of Materials

Cite this

@article{2a56d630a20b41e896039f8d0e13ffc3,
title = "Measurement of solid solubility of warfarin in supercritical carbon dioxide and recrystallization study using supercritical antisolvent process",
abstract = "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 M{\'e}ndez-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.",
keywords = "Solubility, Supercritical antisolvent, Warfarin",
author = "Ciou, {Jheng Ming} and Wang, {Bo Cheng} and Su, {Chie Shaan} and Liu, {Jun Jen} and Sheu, {Ming Thau}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.apt.2017.12.005",
language = "English",
journal = "Advanced Powder Technology",
issn = "0921-8831",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Measurement of solid solubility of warfarin in supercritical carbon dioxide and recrystallization study using supercritical antisolvent process

AU - Ciou, Jheng Ming

AU - Wang, Bo Cheng

AU - Su, Chie Shaan

AU - Liu, Jun Jen

AU - Sheu, Ming Thau

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Solubility

KW - Supercritical antisolvent

KW - Warfarin

UR - http://www.scopus.com/inward/record.url?scp=85042260360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042260360&partnerID=8YFLogxK

U2 - 10.1016/j.apt.2017.12.005

DO - 10.1016/j.apt.2017.12.005

M3 - Article

AN - SCOPUS:85042260360

JO - Advanced Powder Technology

JF - Advanced Powder Technology

SN - 0921-8831

ER -