- 著者
- Takashi Mano Rodney W. Stevens Kazuo Ando Makoto Kawai Kiyoshi Kawamura Kazunari Nakao Yoshiyuki Okumura Takako Okumura Minoru Sakakibara Kimitaka Miyamoto Tetsuya Tamura
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.53, no.8, pp.965-973, 2005 (Released:2005-08-01)
- 参考文献数
- 25
- 被引用文献数
- 15 20
Structural modification of imidazole 5-lipoxygenase (5-LO) inhibitors for optimizing inhibitory potency, pharmacokinetic behavior and toxicity (ocular) profile led to 4-{3-[4-(2-methyl-1H-imidazol-1-yl)phenylthio]}phenyl-3,4,5,6-tetrahydro-2H-pyran-4-carboxamide (6) with no observable ocular toxicity. The orally active and safe imidazole 5-LO inhibitor 6 was selected as a clinical candidate and advanced to clinical studies. An improved synthesis of 6 is also discussed.
- 著者
- Takao Mizumoto Tetsuya Tamura Hitoshi Kawai Atsushi Kajiyama Shigeru Itai
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.56, no.4, pp.530-535, 2008-04-01 (Released:2008-04-01)
- 参考文献数
- 12
- 被引用文献数
- 23 33
In this study, the taste-masking of famotidine, which could apply to any fast-disintegrating tablet, was investigated using the spray-dry method. The target characteristics of taste-masked particles were set as follows: the dissolution rate is not to be more than 30% at 1 min and not less than 85% at 15 min, and the particle size is not to be more than 150 μm in diameter to avoid a gritty feeling in the mouth. The target dissolution profiles of spray-dried particles consisting of Aquacoat ECD30 and Eudragit NE30D or triacetin was accomplished by the screening of formulas and the appropriate lab-scale manufacturing conditions. Lab-scale testing produced taste-masked particles that met the formulation targets. On the pilot scale, spray-dried particles with attributes, such as dissolution rate and particle size, of the same quality were produced, and reproducibility was also confirmed. This confirmed that the spray-dry method produced the most appropriate taste-masked particles for fast-disintegrating dosage forms.