title: Spheronization mechanism of pharmaceutical material crystals processed by extremely high shearing force using a mechanical powder processor.
abstract: 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.
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. Electronic address: kondok@meijo-u.ac.jp.
authors.forename: Keita
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kido
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Niwa
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011208:Powders
chemical_list: D004364:Pharmaceutical Preparations; D011208:Powders
keywords: Layering granulation; Mechanical powder processor; Mechanical spheronization technique; Particle shape modification; Particle strength; Pharmaceutical material; Powder agglomeration; Powder cohesiveness; Spherical crystal