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Controlling the Polymorphism of Indomethacin with Poloxamer 407 in a Gas Antisolvent Crystallization Process

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posted on 2023-01-18, 10:09 authored by Fidel Méndez CañellasFidel Méndez Cañellas, vivek vermavivek verma, Jacek Kujawski, Robert Geertman, Lidia Tajber, Luis PadrelaLuis Padrela

The polymorphic control of active pharmaceutical ingredients (APIs) is a major challenge in the manufacture of medicines. Crystallization methods that use supercritical carbon dioxide as an antisolvent can create unique solid forms of APIs, with a particular tendency to generate metastable polymorphic forms. In this work, the effects of processing conditions within a gas antisolvent (GAS) crystallization method, such as pressure, stirring rate, and temperature, as well as the type of solvent used and the presence of an additive, on the polymorphism of indomethacin were studied. Consistent formation of the X-ray powder diffraction-pure α polymorphic form of indomethacin by GAS was only achieved when a polymer, poloxamer 407, was used as an additive. Using the GAS method in combination with poloxamer 407 as a molecular additive enabled full control over the polymorphic form of indomethacin, regardless of the processing conditions employed, such as pressure, temperature, stirring rate, and type of solvent. A detailed molecular modeling study provided insight into the role of poloxamer 407 in the polymorphic outcome of indomethacin and concluded that it favored the formation of the α polymorph. 

Funding

Long Acting Medicines for Complex Therapeutics Needed Now

European Commission

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CF20170754

Digital metal detector WMC-3

Ministry of Science and Higher Education

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History

Publication

ACS Omega 2022 7 (48), pp. 43945-43957

Publisher

American Chemical Society

Also affiliated with

  • Bernal Institute
  • Synthesis and Solid State Pharmaceutical Centre

Department or School

  • Chemical Sciences

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