Drug recrystallisation using supercritical anti-solvent (SAS) process with impinging jets: effects of process parameters

Abstract : The aim of this study is to improve mixing in supercritical anti-solvent process (SAS) with impinging jets in order to form finer particles of sulfathiazole, a poorly water-soluble drug. The influence of several process parameters upon the powder characteristics is studied. Parameters are jets' velocity (0.25 m/s to 25.92 m/s), molar ratio solvent/CO2 (2.5% to 20%), temperature (313 K to 343 K), pressure (10 MPa to 20 MPa) and sulfathiazole concentration in the organic solution (0.5% to 1.8%). Two solvents are used: acetone and methanol. Smaller particles with a more homogeneous morphology are obtained from acetone solutions. For the smallest jets' velocity, corresponding to a non-atomized jet, the stable polymorphic form is obtained, pure or in mixture. At this velocity, pressure is the most influential parameter controlling the polymorphic nature of the powder formed. The pure stable polymorph is formed at 20 MPa. Concerning the particle size, the most influential parameters are temperature and sulfathiazole concentration. The use of impinging jets with different process parameters allows the crystallization of four polymorphs among the five known, and particle sizes are varied. This work demonstrates the studied device ability of the polymorph and the size control. A comparison with the classical SAS process shows that particle size, size distribution and morphology of particles crystallized with impinging jets are different from the ones obtained with classical SAS introduction device in similar operating conditions. Mean particle sizes are significantly smaller and size distributions are narrower with impinging jets device.
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Stéphanie Careno, Olivier Boutin, Elisabeth Badens. Drug recrystallisation using supercritical anti-solvent (SAS) process with impinging jets: effects of process parameters. Journal of Crystal Growth, Elsevier, 2012, 342 (1), pp.34-41. ⟨10.1016/j.jcrysgro.2011.06.059⟩. ⟨hal-00993004⟩



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