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Investigation of the Particle Growth of Fenofibrate following Antisolvent Precipitation and Freeze-Drying
University of Limerick.ORCID iD: 0000-0003-1790-2310
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2015 (English)In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 15, no 11, p. 5213-5222Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2015. Vol. 15, no 11, p. 5213-5222
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:kth:diva-260110DOI: 10.1021/acs.cgd.5b00662ISI: 000364356000007Scopus ID: 2-s2.0-84946430347OAI: oai:DiVA.org:kth-260110DiVA, id: diva2:1355960
Note

Cited By :13; Export Date: 25 September 2019

QC 20191030

Available from: 2019-09-30 Created: 2019-09-30 Last updated: 2019-10-30Bibliographically approved

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