Pharmaceutical co-crystals of the anti-inflammatory drug diflunisal and nicotinamide obtained using supercritical CO2 as an antisolvent
(2016) In Journal of CO2 Utilization 13. p.29-37- Abstract
A method based on using supercritical CO2 as an antisolvent (SAS method) is explored as a co-crystallization technique. Co-crystallization is an emerging and powerful technique to improve the physicochemical properties of an active pharmaceutical ingredient. The solid-state and solution co-crystallization methods usually employed present several disadvantages. The one-step SAS method has a low environmental impact and overcomes some of the difficulties associated to conventional methods. The 2:1 co-crystals of the anti-inflammatory drug diflunisal (DIF) and nicotinamide (NIC) are prepared for the first time by SAS. Drug concentrations corresponding to the co-crystal stoichiometric composition are used. The influence of the... (More)
A method based on using supercritical CO2 as an antisolvent (SAS method) is explored as a co-crystallization technique. Co-crystallization is an emerging and powerful technique to improve the physicochemical properties of an active pharmaceutical ingredient. The solid-state and solution co-crystallization methods usually employed present several disadvantages. The one-step SAS method has a low environmental impact and overcomes some of the difficulties associated to conventional methods. The 2:1 co-crystals of the anti-inflammatory drug diflunisal (DIF) and nicotinamide (NIC) are prepared for the first time by SAS. Drug concentrations corresponding to the co-crystal stoichiometric composition are used. The influence of the SAS parameters temperature (35 and 40 °C), pressure (10.0 and 12.0 MPa), drug concentration (two levels) and solvent (acetone and ethanol) in the co-crystal formation is studied. A crystalline material in the form of needles of uniform width and more variable length is obtained. For comparison purposes, pure DIF and NIC are also processed by SAS. Co-crystals are characterized in terms of crystallinity, thermal behavior, coformer interactions and drug release; their dissolution rate improves with respect to that of pure DIF. SAS co-crystals exhibit the same crystal structure, melting point and FTIR spectrum as those previously obtained by liquid assisted ball mill grinding and solution crystallization.
(Less)
- author
- Cuadra, Isaac A. ; Cabañas, Albertina ; Cheda, José A R ; Martinez, Francisco LU and Pando, Concepción
- organization
- publishing date
- 2016-03-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Carbon dioxide, Nicotinamide, Pharmaceutical co-crystals, Supercritical antisolvent diflunisal
- in
- Journal of CO2 Utilization
- volume
- 13
- pages
- 9 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:84949604564
- wos:000370331600004
- ISSN
- 2212-9820
- DOI
- 10.1016/j.jcou.2015.11.006
- language
- English
- LU publication?
- yes
- id
- 1dc2b9a6-3f73-4082-9f8f-9e52af6a34a1
- date added to LUP
- 2016-07-26 08:57:47
- date last changed
- 2024-04-05 02:40:53
@article{1dc2b9a6-3f73-4082-9f8f-9e52af6a34a1,
abstract = {{<p>A method based on using supercritical CO<sub>2</sub> as an antisolvent (SAS method) is explored as a co-crystallization technique. Co-crystallization is an emerging and powerful technique to improve the physicochemical properties of an active pharmaceutical ingredient. The solid-state and solution co-crystallization methods usually employed present several disadvantages. The one-step SAS method has a low environmental impact and overcomes some of the difficulties associated to conventional methods. The 2:1 co-crystals of the anti-inflammatory drug diflunisal (DIF) and nicotinamide (NIC) are prepared for the first time by SAS. Drug concentrations corresponding to the co-crystal stoichiometric composition are used. The influence of the SAS parameters temperature (35 and 40 °C), pressure (10.0 and 12.0 MPa), drug concentration (two levels) and solvent (acetone and ethanol) in the co-crystal formation is studied. A crystalline material in the form of needles of uniform width and more variable length is obtained. For comparison purposes, pure DIF and NIC are also processed by SAS. Co-crystals are characterized in terms of crystallinity, thermal behavior, coformer interactions and drug release; their dissolution rate improves with respect to that of pure DIF. SAS co-crystals exhibit the same crystal structure, melting point and FTIR spectrum as those previously obtained by liquid assisted ball mill grinding and solution crystallization.</p>}},
author = {{Cuadra, Isaac A. and Cabañas, Albertina and Cheda, José A R and Martinez, Francisco and Pando, Concepción}},
issn = {{2212-9820}},
keywords = {{Carbon dioxide; Nicotinamide; Pharmaceutical co-crystals; Supercritical antisolvent diflunisal}},
language = {{eng}},
month = {{03}},
pages = {{29--37}},
publisher = {{Elsevier}},
series = {{Journal of CO2 Utilization}},
title = {{Pharmaceutical co-crystals of the anti-inflammatory drug diflunisal and nicotinamide obtained using supercritical CO<sub>2</sub> as an antisolvent}},
url = {{http://dx.doi.org/10.1016/j.jcou.2015.11.006}},
doi = {{10.1016/j.jcou.2015.11.006}},
volume = {{13}},
year = {{2016}},
}