1 0 0 0 OA 新規抗生物質E1040の固体安定性と製剤化研究について
- 著者
- 芦澤 一英 内川 清彦 服部 禎一 石橋 泰雄 三宅 康夫 里 忠
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.110, no.3, pp.191-201, 1990-03-25 (Released:2008-05-30)
- 参考文献数
- 45
- 被引用文献数
- 1 2
In designing the dosage form, one major factor controling their physicochemical properties is solid forms of the drug powder. The method for improving the physicochemical stability of unstable β-lactam antibiotics is very important. E1040 is a novel parenteral 3-betaine type cephalosporin which has a broad antibacterial spectrum and potent activities against Citrobacter, freundii, Enterobacter cloacase, and glucose-nonfermentative bacteria, including P. aeruginosa. The present study was intended to provide the solid-state chemical stability of perenteral steril dry dosage form of E1040. The chemical stability differences among the various solid forms, dry amorphous, additive freeze dried amorphous solid and crystalline powder, were evaluated as a function of temperature by thermo stress tests. Freeze dried anhydrous amorphous form was the first steril dry dosage form investigated during the preformulation study. However, this compound is chemically unstable, in the titer of them, reduction are observed in the freeze dried amorphous solid. In order to select the most suitable solid form of E1040, two methods were used. One was crystalline solid and the other was NaCl additive freezedried formulation. Through our experiments, the solid-state chemical stabilization can be achieved by these two methods (effect of crystal structure and effect of NaCl additive).
1 0 0 0 OA X線回折と光音響赤外スペクトル測定法によるE1040結晶の結晶化度の評価について
- 著者
- 芦澤 一英 内川 清彦 服部 禎一 石橋 泰雄 三宅 康夫 里 忠
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.110, no.3, pp.202-209, 1990-03-25 (Released:2008-05-30)
- 参考文献数
- 34
An X-ray diffraction methods and Fourier transform infrared analysis with photoacoustic detector (FTIR-PAS) for estimation of the degree of crystallinity of crystalline E1040 formulation was established. The X-ray procedure to determine the crystallinity of E1040 was based upon the measurement of the total scattering and the scattering from the crystalline region of the drug. The FTIR-PAS procedures are based upon the measurement of the peak height ratio at 1628 cm-1 and measurement of the spectral region between 2400 and 3700 cm-1 by the Partial least squares (PLS) techniques. The data of the degree of crystallinity from the X-ray diffraction methods are consistent with the data from FTIR-PAS methods. The increase of the degree of crystallinity of the drug formulation decreased the decomposition rate of E1040. As a result, it had become apparent that two analytical procedures were actually valid. This assured optimizing process conditions which affect the improvement of crystallinity.