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Pharmaceutical co-crystals of the anti-inflammatory drug diflunisal and nicotinamide obtained using supercritical CO2 as an antisolvent

Cuadra, Isaac A.; Cabañas, Albertina; Cheda, José A R; Martinez, Francisco LU and Pando, Concepción (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.

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author
organization
publishing date
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
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
2016-11-20 04:34:58
@misc{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},
  keyword      = {Carbon dioxide,Nicotinamide,Pharmaceutical co-crystals,Supercritical antisolvent diflunisal},
  language     = {eng},
  month        = {03},
  pages        = {29--37},
  publisher    = {ARRAY(0x8ffcb70)},
  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},
  volume       = {13},
  year         = {2016},
}