Jump to ContentJump to Main Navigation

Online

49,00 € / $74.00*

* Prices subject to change. Shipping costs will be added if applicable.
Publication Date:
September 2007
ISSN:
1542-6580
DOI:
10.2202/1542-6580.1435

See all formats and pricing

Online
Individual Subscription Online only
Euro [D] 49.00
RRP for USA, Canada, Mexico
US$ 74.00 *
Print
Individual Subscription Online only
Euro [D] 218.00
RRP for USA, Canada, Mexico
US$ 294.00 *
Print + Online
Individual Subscription Online only
Euro [D] 262.00
RRP for USA, Canada, Mexico
US$ 353.00 *
*Prices subject to change. Shipping costs will be added if applicable.

New Journal at De Gruyter!

Ed. by de Lasa, Hugo / Xu, Charles

1 Issue per year

Increased IMPACT FACTOR 2011: 0.790

 

Crystallization of Drugs using Supercritical CO2 as Antisolvent: From Phase Equilibria to Products

Pascale Subra-Paternault1 / Christelle Roy2 / Arlette Vega-Gonzalez3 / Patrick Jestin4

1Université de Bordeaux, subra@enscpb.fr

2Université Paris 13, roy@limhp.univ-paris13.fr

3Université Paris 13, vega@limhp.univ-paris13.fr

4Université Paris 13, jestin@limhp.univ-paris13.fr

Citation Information: International Journal of Chemical Reactor Engineering. Volume 5, Issue 1, Pages –, ISSN (Online) 1542-6580, DOI: 10.2202/1542-6580.1435, September 2007

Publication History:
Published Online:
2007-09-12

The demand for green technologies is continually increasing due to the growing consciousness of alimentary, environmental and toxicity risks. Supercritical technologies have beneficed from that interest and have therefore received increased attention as propitious media for elaboration of materials in general and formation of particles in particular, especially for pharmaceutical applications. This work presents the recrystallization of several drugs from liquid organic solutions, using CO2 as the precipitating agent. Three drugs were specially studied: theophylline, tolbutamide and griseofulvin. To select the suitable process among the several potentialities offered by SCF and to further understand and interpret the crystallization behaviour, selected phase behaviour of binary and ternary systems involving solute-solvent-CO2 were investigated and are presented hereby as background. Drugs were further precipitated by compressed CO2 as antisolvent, and experimental data focused mostly on results obtained in the discontinuous stirred version of the process. There was special emphasis on the influence of stirring and CO2 introduction rates upon the crystals characteristics and the production yields. The main difference between the investigated drug-solvent systems was their sensitivity to the stirring. As a first step, macro- and micro-mixing times were estimated; it was shown that mixing times due to circulation and to molecular diffusion were in the same range, with no significant breakthrough as a function of the solvent. Since the large size of particles produced by batch might be detrimental for therapeutic applications and/or administration routes, several precipitations were performed in the semi-continuous mode. Conditions were varied in order to play with phase behaviour, i.e. by setting the pressure below or above the critical locus of the solvent-CO2 system. Morphology of particles suggested that precipitation was confined within the solvent droplets, originating smaller precipitates than particles produced at monophasic conditions. The results obtained for three systems show that size of precipitates can be manipulated by a proper selection of thermodynamics and time or space scales, although the later has to be more accurately investigated to view the two versions of the antisolvent processes as complementary.

Keywords: supercritical; antisolvent; crystallization; phase behaviour; stirring; continuous operation

Comments (0)

Please log in or register to comment.