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Crystals
Article . 2024 . Peer-reviewed
License: CC BY
Data sources: Crossref
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Crystals
Article . 2024
Data sources: DOAJ
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Modification of Ceritinib Crystal Morphology via Spherical Crystallization

Authors: Iva Zokić; Jasna Prlić Kardum; Lana Crnac; Mirta Sabol; Juraj Vuić; Valentina Travančić;

Modification of Ceritinib Crystal Morphology via Spherical Crystallization

Abstract

The formulation process for some drugs can be challenging, due to their unfavorable physical and mechanical properties and poor water solubility. Powder technology has made a significant impact in regard to the modification of the particles in active pharmaceutical ingredients (APIs) to produce high-quality granules. Spherical particles are preferred over other shapes, due to their high tap and bulk density, reduced dustiness, better flowability, strong anti-caking properties, and better mechanical performance during tableting. The present study investigates the possibility of obtaining spherical crystals of ceritinib, a drug used for the treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer, which belongs to BCS class IV drugs and has a platy crystal shape. Ceritinib spheres were prepared by spherical agglomeration, in a ternary system, and quasi-emulsion solvent diffusion, with the addition of polyvinylpyrrolidone, as well as a combination of these two methods. With the combined method of spherical crystallization, crystals with the most favorable morphology and the narrowest distribution of particle sizes were obtained, which was the reason for further optimization. The influence of different impeller geometries and mixing rates on the morphology of the obtained crystals was examined and the optimal conditions for the process were selected. Using empirical correlations and a visual criterion, the process was scaled up from a 0.1 L to a 1 L batch crystallizer. The obtained crystals were characterized by light and scanning electron microscopy. The addition of a bridging liquid and/or a polymer additive did not change the internal structure of the ceritinib crystals, which was confirmed by X-ray powder diffraction.

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Keywords

spherical crystallization, Crystallography, QD901-999, active pharmaceutical ingredient, ceritinib, scale up

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
2
Top 10%
Average
Average
gold
Related to Research communities
Cancer Research