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Optimizing the crystal size and habit of β-sitosterol in suspension

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Abstract

The aim of this work was to survey how processing parameters affect the crystal growth of β-sitosterol in suspension. The process variables studied were the cooling temperature, stirring time and stirring rate during recrystallization. In addition, we investigated the effect a commonly used surfactant, polysorbate 80, has on crystal size distribution and the polymorphic form. This study describes the optimization of the crystallization process, with the object of preparing crystals as small as possible. Particle size distribution and habit were analyzed using optical microscopy, and the crystal structure was analyzed using X-ray diffractometry. The cooling temperature had a remarkable influence on the crystal size. Crystals with a median crystal length of ≈23 μm were achieved with a low cooling temperature (<10°C); however, a fairly large number of crystals over 50 μm appeared. Higher cooling temperatures (>30°C) caused notable crystal growth both in length and width. Rapid (250 rpm), continuous stirring until the suspensions had cooled to room temperature created small, less than 50 μm long (median <20 μm), needle-shaped crystals. The addition of surfactant slightly reduced the size of the initially large crystals. Both hemihydrate and monohydrate crystal forms occurred throughout, regardless of the processing parameters. By using an optimized process, it was possible to obtain a microcrystalline suspension, with a smooth texture.

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Authors and Affiliations

  1. Technology Division, Department of Pharmacy, University of Helsinki, Finland

    Anna von Bonsdorff-Nikander, Leena Christiansen & Jouko Yliruusi

  2. Viikki Drug Discovery Technology Center (DDTC), University of Helsinki, Finland

    Jukka Rantanen & Jouko Yliruusi

Authors
  1. Anna von Bonsdorff-Nikander
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  2. Jukka Rantanen
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  3. Leena Christiansen
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  4. Jouko Yliruusi
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Correspondence to Anna von Bonsdorff-Nikander.

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von Bonsdorff-Nikander, A., Rantanen, J., Christiansen, L. et al. Optimizing the crystal size and habit of β-sitosterol in suspension. AAPS PharmSciTech 4, 44 (2003). https://doi.org/10.1208/pt040344

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  • DOI: https://doi.org/10.1208/pt040344

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