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Investigation of the particle growth of fenofibrate following antisolvent precipitation and freeze-drying

journal contribution
posted on 2022-08-24, 15:12 authored by Teresa B. Tierney, Yina Guo, SERGEY BELOSHAPKINSERGEY BELOSHAPKIN, Åke RasmusonÅke Rasmuson, SARAH HUDSONSARAH HUDSON
Submicron to small-micron-sized particles of the hydrophobic drug, fenofibrate, were prepared by controlled crystallization in order to influence its dissolution behavior. An antisolvent precipitation process successfully generated particles (200-300 nm) which matched the size and dissolution behavior of a commercial wet-milled formulation of the drug. Although the preparation of submicron-sized particles was straightforward, retaining their size in suspension and during isolation was a challenge. Additives were employed to temporarily stabilize the suspension, and extend the time window for isolation of the submicron particles. Precipitated particles were isolated primarily by immediate freeze-drying, but drying stresses were found to destabilize the fragile submicron system. The growth pathway of particles in suspension and during oven and freeze-drying were compared. Although the growth pathways appeared considerably different from a visual morphological perspective, an investigation of the electron diffraction patterns and the inner-particle surfaces showed that the growth pathways were the same: molecular addition by Ostwald ripening. The observed differences in the time-resolved particle morphologies were found to be a result of the freeze-drying process.

Funding

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History

Publication

Crystal Growth and Design;15 (1), pp. 5213-5222

Publisher

American Chemical Society

Note

peer-reviewed

Other Funding information

IRC, ERC, Program for Research in Third-Level Institutions (PRTLI) Cycle 5

Rights

© 2015 ACS This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal Title, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.cgd.5b00662

Language

English

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