Effect of impurity concentration on the precipitation of atorvastatin calcium under microgravity on the International Space Station

• Published in: Colloids and surfaces. A, Physicochemical and engineering aspects Vol. 700; p. 134553
• Main Authors: Otsuka, Makoto, Kuroyanagi, Yota, Sasaki, Tetsuo, Matsumoto, Masakazu, Asamoto, Hiromichi, Hirose, Yutaro, Tanaka, Hiroaki, Sato, Naohiro
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.11.2024
• Subjects: Atorvastatin calcium; Counter-diffusion cell method; Crystal morphology; International Space Station; Microgravity and normal gravity conditions; Multivariable analysis; Precipitation with impurity; Raman spectroscopic microscopy; Precipitation with impurity; Atorvastatin calcium; Microgravity and normal gravity conditions; International Space Station; Crystal morphology; Counter-diffusion cell method; Raman spectroscopic microscopy; Multivariable analysis
• ISSN: 0927-7757
• DOI: 10.1016/j.colsurfa.2024.134553

The influence of the concentration of impurities on the precipitation of atorvastatin calcium (ATC) under microgravity conditions at the International Space Station was investigated. An ATC mixture containing 0.0, 0.1, 0.3, or 1.0 % w/w of rosuvastatin calcium as an impurity was added to methanol, which readily dissolved the compounds. Microcapillaries filled with the ATC mother liquor were loaded into counter-diffusion cell tubes filled with pure water, a poor solvent for the mixture, and prepared as ATC mother liquor. The counter-diffusion cell tubes were placed in a warming device and launched to the International Space Station aboard a rocket. After 30 days of precipitation under microgravity, the solids were separated from the liquids, and their Raman spectra were measured. The Raman spectra of the orbited and control solid samples, precipitated under microgravity and normal gravity, respectively, displayed different peak intensities depending on the impurity. To demonstrate the effect of microgravity on ATC precipitation, Raman spectra of ATC precipitated with and without the impurity under microgravity and normal gravity were analyzed using principal component analysis. The Raman spectra were also quantitatively analyzed using partial least squares regression, for which the impurity was the objective variable, to investigate the intermolecular interactions between ATC and the impurity during precipitation. Microgravity was found to affect the crystal morphology and precipitation of impurity-containing ATC. [Display omitted]