Nonclassical Crystallization and Core-Shell Structure Formation of Ibuprofen from Binary Solvent Solutions

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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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Crystal Growth and Design, Volume 23, issue 1
Liquid-liquidphase separation (LLPS) or dense liquid intermediates during the crystallization of pharmaceutical molecules is common; however, their role in alternative nucleation mechanisms is less understood. Herein, we report the formation of a dense liquid intermediate followed by a core-shell structure of ibuprofen crystals via nonclassical crystallization. The Raman and SAXS results of the dense phase uncover the molecular structural ordering and its role in nucleation. In addition to the dimer formation of ibuprofen, which is commonly observed in the solution phase, methyl group vibrations in the Raman spectra show intermolecular interactions similar to those in the solid phase. The SAXS data validate the cluster size differences in the supersaturated solution and dense phase. The focused-ion beam cut image shows the attachment of nanoparticles, and we proposed a possible mechanism for the transformation from the dense phase into a core-shell structure. The unstable phase or polycrystalline core and itssubsequent dissolution from inside to outside or recrystallization by reversed crystal growth produces the core-shell structure. The LLPS intermediate followed by the core-shell structure and its dissolution enhancement unfold a new perspective of ibuprofen crystallization.
| openaire: EC/H2020/842140/EU//OMECRY Funding Information: R.M. thanks the European Union for financial support for this work under the H2020-Marie Skłodowska-Curie Individual Fellowship (grant agreement No [842140]). He also thanks the Bioeconomy and RawMatters Research Infrastructures and OtaNano Nanomicroscopy Center, Aalto University, Finland, for the research facilities. Publisher Copyright: © 2022 The Authors. Published by American Chemical Society.
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Mani , R , Peltonen , L , Strachan , C J , Karppinen , M & Louhi-Kultanen , M 2023 , ' Nonclassical Crystallization and Core-Shell Structure Formation of Ibuprofen from Binary Solvent Solutions ' , Crystal Growth and Design , vol. 23 , no. 1 , pp. 236-245 .