Understanding morphological evolution of Griseofulvin particles into hierarchical microstructures during liquid antisolvent precipitation

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dc.contributor.author Prasad, Rupanjali
dc.contributor.author Dalvi, Sameer V.
dc.date.accessioned 2019-09-25T12:21:58Z
dc.date.available 2019-09-25T12:21:58Z
dc.date.issued 2019-09
dc.identifier.citation Prasad, Rupanjali and Dalvi, Sameer V., "Understanding morphological evolution of Griseofulvin particles into hierarchical microstructures during liquid antisolvent precipitation", Crystal Growth & Design, DOI: 10.1021/acs.cgd.9b00859, Sep. 2019. en_US
dc.identifier.issn 1528-7483
dc.identifier.issn 1528-7505
dc.identifier.uri http://dx.doi.org/10.1021/acs.cgd.9b00859
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/4844
dc.description.abstract Controlling morphology of active pharmaceutical ingredients (APIs) during crystallization/precipitation is essential for pharmaceutical development since the pharmaceutical powder properties such as solubility, flowability, and dissolution rates are morphology dependent. The objective of this work was to understand the morphological evolution of a poorly water-soluble antifungal drug, griseofulvin (GF), during liquid antisolvent (LAS) precipitation in the presence of ultrasound and additives. GF was found to precipitate as hierarchical structures in the presence of different additives and in the absence of ultrasound. An umbrella-like morphology was observed when hydroxypropyl methylcellulose was used, hexagonal particles elongated along the central axis were obtained in the presence of Tween 80, and the use of polyvinylpyrrolidone yielded long needle-like particles. The most fascinating morphology was observed in the case of bovine serum albumin and no ultrasound, where the GF particles precipitated as six-branched hierarchical structures. Interestingly, the morphology of 6-month-old GF particles reveals that the outline of the overall morphology of initial unfilled skeletons resembled the bipyramidal morphology that would form when particles are completely filled/fused due to Ostwald ripening. The size of GF particles typically varied from 30 to 50 ?m when no ultrasound was used. Time-resolved scanning electron microscopy (SEM) studies imply that interesting morphologies of GF particles observed in the absence of ultrasound could be the result of aggregation and fusion of a large number of small particles formed in the beginning of the precipitation process. These smaller particles fuse to form primary bipyramidal particles which then undergo diffusion-limited growth through Ostwald ripening and secondary nucleation on specific particle faces due to selective adsorption of additives depending on the functional groups present on those particular faces. In contrast to the no ultrasound situation, the use of ultrasound along with the additives resulted in the formation of completely filled octahedron/bipyramidal GF particles irrespective of the additive used. These particles were significantly smaller with sizes ranging from 4 to 6 ?m. Use of ultrasound improves micromixing and alters the particle growth mechanism from diffusion limited to integration controlled resulting in smaller and well-formed GF particles.
dc.description.statementofresponsibility by Rupanjali Prasad and Sameer V. Dalvi
dc.language.iso en_US en_US
dc.publisher American Chemical Society en_US
dc.title Understanding morphological evolution of Griseofulvin particles into hierarchical microstructures during liquid antisolvent precipitation en_US
dc.type Article en_US
dc.relation.journal Crystal Growth & Design


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