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Precipitation of pharmaceuticals using a supercritical anti-solvent (SAS) dechnique: A preliminary study

Authors

  • Photchanathip Imsanguan,

    1. Faculty of Engineering, Department of Chemical Engineering, King Mongkut's University of Technology Thonburi, Bangkok 10140, Thailand
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  • Tanawan Yanothai,

    1. Faculty of Engineering, Department of Chemical Engineering, King Mongkut's University of Technology Thonburi, Bangkok 10140, Thailand
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  • Suwassa Pongamphai,

    Corresponding author
    1. Faculty of Engineering, Department of Chemical Engineering, King Mongkut's University of Technology Thonburi, Bangkok 10140, Thailand
    • Faculty of Engineering, Department of Chemical Engineering, King Mongkut's University of Technology Thonburi, Bangkok 10140, Thailand.
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  • Supaporn Douglas,

    1. Faculty of Engineering, Department of Chemical Engineering, King Mongkut's University of Technology Thonburi, Bangkok 10140, Thailand
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  • Wittaya Teppaitoon,

    1. Faculty of Engineering, Department of Chemical Engineering, King Mongkut's University of Technology Thonburi, Bangkok 10140, Thailand
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  • Peter L. Douglas

    1. Department of Chemical Engineering, University of Waterloo, Ontario, Canada N2L 3G1
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Abstract

The aims of this research were to investigate the applicability of the supercritical anti-solvent (SAS) process on the precipitation of pharmaceuticals (andrographolide and acetaminophen). In particular, the goal of this research was to study the influence of pressure at 10 and 24 MPa on particle characteristics (morphology, crystalline structure, polymorphic form, size, size distribution, and precipitation yield), and to compare the precipitation efficiency of SAS process and evaporation process. Scanning electron microscope (SEM), X-ray diffraction (XRD), and high performance liquid chromatography (HPLC) showed a significant change in particle size, size distribution, morphology, and precipitation yield, respectively. From an analysis of the results it was found that the crystal size of andrographolide and acetaminophen decreased with increasing pressure. The morphology of andrographolide particles changed from slice-like to column-like when the pressure was increased. On the other hand, the acetaminophen particles obtained were found to be monoclinic form (I) under both operating pressures. The SAS process produced small uniform shaped crystals, with a narrow size distribution, high precipitation yield and selective precipitation were also observed.

Abstract

L'objectif de cette recherche est d'examiner si le procédé par antisolvant supercritique (ASS) est applicable à la précipitation de produits pharmaceutiques (andrographolide et acétaminophène) et d'évaluer l'influence des pressions de service (10 MPa et 24 MPa) sur la morphologie, la taille des particules, la répartition des éléments et le rendement de précipitation. Le rendement de précipitation du procédé par ASS a également été comparé à celui du procédé par évaporation. La microscopie électronique à balayage (MEB) associée au logiciel Image-Pro Plus, la diffractométrie de rayons X (DRX) et la chromatographie liquide à haute performance (CLHP) ont montré des différences importantes sur le plan de la morphologie, de la taille des particules, de la répartition des tailles et du rendement de précipitation, respectivement. Les résultats semblent indiquer que la taille des cristaux d'andrographolide et d'acétaminophène diminue lorsque la pression augmente. La morphologie des particules d'andrographolide est passée d'une forme de strate à une forme de colonne avec l'augmentation de la pression. En revanche, selon les résultats, les particules d'acétaminophène obtenues ont une forme monoclinique (I) avec les deux pressions de service. Le procédé par ASS produit des cristaux uniformes, des particules de petite taille, une faible répartition des particules, un rendement de précipitation élevé ainsi qu'une précipitation sélective.

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