Optimizing the crystal size and habit of beta-sitosterol in suspension.
The aim of this work was to survey how processing parameters affect the crystal growth of beta-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 approximately 23 microm were achieved with a low cooling temperature (<10 degrees C); however, a fairly large number of crystals over 50 microm appeared. Higher cooling temperatures (>30 degrees 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 micro m long (median <20 microm), 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.
von Bonsdorff-Nikander
Anna
A
Pharmaceutical Technology Division, Department of Pharmacy, University of Helsinki, Finland. anna.vonbonsdorff@helsinki.fi
Rantanen
Jukka
J
Christiansen
Leena
L
Yliruusi
Jouko
J
D002626:Chemistry, Pharmaceutical; D003080:Cold Temperature; D003460:Crystallization / Q000379:methods; D010316:Particle Size; D012855:Sitosterols / Q000737:chemistry* / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism; D013535:Suspensions / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014961:X-Ray Diffraction / Q000379:methods
D012855:Sitosterols; D013501:Surface-Active Agents; D013535:Suspensions; C025473:gamma-sitosterol