Kondo Keita, Kido Keisuke, Niwa Toshiyuki
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
Eur J Pharm Biopharm. 2016 Oct;107:7-15. doi: 10.1016/j.ejpb.2016.06.021. Epub 2016 Jun 28.
We aimed to elucidate the mechanism of the spheronization of pharmaceutical material crystals through extremely high shearing force using a mechanical powder processor, which produces spherical crystals without a solvent. The spheronization of theophylline, acetaminophen, clarithromycin, ascorbic acid and lactose was investigated, and the relationship between the spheronization mechanism and material characteristics was also examined. Theophylline and ascorbic acid crystals were partially destroyed during mechanical processing, yielding large particles and dust, and the large fragments were then layered with powder to produce spheres with a core-shell structure. Acetaminophen crystals were completely fragmented under stress, yielding fine particles to which powder then agglomerated to produce spheres with a mosaic structure. Clarithromycin and lactose crystals were not spheronized. Our results showed that the fracture strength of intact material may be closely related to the size of intermediate fragments, determining spheronization mechanism. Furthermore, the results for powder cohesiveness suggest that the materials with moderate-to-high cohesiveness (theophylline, acetaminophen and ascorbic acid) are finally spheronized regardless of the degree of the strength, whereas those with low cohesiveness (clarithromycin and lactose) are not spheronized due to poor granulation. Hence, the cohesiveness of a material has a significant effect on the success of mechanical spheronization processes.
我们旨在通过使用机械粉末处理器施加极高剪切力来阐明药物材料晶体球化的机制，该处理器可在无溶剂的情况下生产球形晶体。研究了茶碱、对乙酰氨基酚、克拉霉素、抗坏血酸和乳糖的球化情况，并考察了球化机制与材料特性之间的关系。在机械加工过程中，茶碱和抗坏血酸晶体部分被破坏，产生大颗粒和粉尘，然后大碎片被粉末包覆形成核壳结构的球体。对乙酰氨基酚晶体在应力作用下完全破碎，产生细颗粒，粉末随后聚集在这些细颗粒上形成镶嵌结构的球体。克拉霉素和乳糖晶体未发生球化。我们的结果表明，完整材料的断裂强度可能与中间碎片的大小密切相关，从而决定球化机制。此外，粉末粘性的结果表明，具有中等到高粘性的材料（茶碱、对乙酰氨基酚和抗坏血酸）无论强度如何最终都会球化，而粘性低的材料（克拉霉素和乳糖）由于造粒性差而不会球化。因此，材料的粘性对机械球化过程的成功有显著影响。
