Towards controlling the crystallisation behaviour of fenofibrate melt: triggers of crystallisation and polymorphic transformation

Tipduangta, Pratchaya, Takieddin, Khaled, Fábián, László, Belton, Peter and Qi, Sheng (2018) Towards controlling the crystallisation behaviour of fenofibrate melt: triggers of crystallisation and polymorphic transformation. RSC Advances, 8 (24). pp. 13513-13525. ISSN 2046-2069

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Abstract

Fenofibrate (FEN) is a dyslipidemia treatment agent which is poorly soluble in water. FEN has tendency to form polymorphs and its crystallisation behaviour is difficult to predict. The nucleation process can be initiated by mechanical disruption such as ball milling or surface scratching which may result in different crystallisation behaviour to that observed in the unperturbed system. This study has obtained insights into the controllability of FEN crystallisation by means of regulating the exposed surface and growth temperatures during its crystallisation. The availability of an open top surface (OTS) during the crystallisation of the FEN melt resulted in a mixture containing FEN form I and IIa (I ≫ IIa) at room temperature, and in the range 40 to 70 °C. Covering the surface led to significant increases in the yield of form IIa at room temperature and at 40 and 50 °C. These temperatures also yielded the highest amount of form IIa in the OTS samples whilst crystallisation at 70 °C led to only FEN form I crystals regardless of the availability of the free surface. The metastable FEN form IIa transforms to the stable form I under the influence of a mechanical stress. Additionally, the introduction of OTS before the completion of crystallisation of form IIa led to a ‘switch’ of from IIa growth to form I. This study demonstrates that the polymorph selection of FEN can be obtained by the manipulation of the crystallisation conditions.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy

Faculty of Science > School of Chemistry
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Depositing User: Pure Connector
Date Deposited: 19 Apr 2018 12:30
Last Modified: 22 Apr 2020 06:34
URI: https://ueaeprints.uea.ac.uk/id/eprint/66813
DOI: 10.1039/C8RA01182F

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