Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10147988 | Journal of Crystal Growth | 2018 | 7 Pages |
Abstract
We improved the crystal quality of the metastable phase of a pharmaceutical compound acetaminophen (form II) using solution-mediated phase transformation (SMPT) combined with the control of supersaturation and crystal size. Form II crystals grew at low supersaturation via SMPT of the trihydrate at low temperature (10â¯Â°C). While crystal growth rate was low compared to the 20â¯Â°C condition, crystals had many defects such as solution inclusions or cracks at 20â¯Â°C, but few at 10â¯Â°C. The ratio of form II crystals with any defects was small (12%), about 1/3 that of the 20â¯Â°C condition. Since the concentration gradient on the crystal surface was relatively small at low bulk supersaturation, high-quality crystals grew uniformly. However, large crystals (>â¼0.8â¯mm) were still defective even at low supersaturation, because concentration gradient is large on large surfaces. Using a new seed-dipping process, obtained crystals were small and uniform in size (â¼0.4â¯mm), and the ratio of defective crystals was reduced to 6%. Powder X-ray diffraction analysis revealed that form II crystals were â¼6 times more temporally stable than in the 20â¯Â°C condition. We found that high-quality crystals of metastable phase with high temporal stability could be realized by low supersaturation and reduction of the crystal size via SMPT.
Keywords
Related Topics
Physical Sciences and Engineering
Physics and Astronomy
Condensed Matter Physics
Authors
Riki Fujimoto, Mihoko Maruyama, Yoichiro Mori, Shino Okada, Hiroaki Adachi, Hiroshi Y. Yoshikawa, Kazufumi Takano, Satoshi Murakami, Hiroyoshi Matsumura, Tsuyoshi Inoue, Masayuki Imanishi, Katsuo Tsukamoto, Masashi Yoshimura, Yusuke Mori,