Pseudopolymorphism and phase stability in four solid forms of (6R,7R)-7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-(Z)-2-methoxy-iminoacetamid]-3-[(4-carbamoyl-1-quinuclidinio)methyl]-8-oxo-5-thia-l-azabicyclo-[4,2,0]oct-2-ene-2-carboxylate (E1040)

✍ Scribed by Kazuhide Ashizawa; Kiyohiko Uchikawa; Teiichi Hattori; Yasuo Ishibashi; Tadashi Sato; Yasuo Miyake

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 967 KB
• Volume: 78
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600781103

✦ Synopsis

0 (6R,7R)-7-[2-(5-Amir1o-l,2,4-thiadiazol9-yl)-(Z)-2-methoxyiminoacetamid]-3-[(4-carbamoyl-1 -quinuclidinio)methylJ-8-oxo-5thia-1 -azabicyclo [4,2,0]oct-2-ene-2-carboxylate (1 ; E l 040) was isolated as a-(decahydralte), p-(pentahydrate), and yform (anhydrate) crystals and the X-ray amorphous form. The relationship between the pseudopolymorphic crystal forms of this compound and water content was studied by X-ray diffractometry, coulometric moisture analysis, thermal analysis, and hygroscopic and vacuum-freeze-drying experiments. The phase transition of crystalline 1 clearly indicated the effect of water content on dehydration. During dehydration, hydrated a-form (decahydrate) crystals and p-form (pentahydrate) crystals became anhydrate yforin crystals, with the diffraction angle shifting toward shorter spacing ;accompanied by line broadening. These results indicate conversion of hydrate 1 crystals to the anhydrous form and contraction of the crystal lattice. It was estimated that the decahydrate (a-form) crystals contain 8 molimol crystal water and 2 molimol adhesion water, and that the pentahydrate (p-form) crystals contain 4 molimol crystal water and 1 molimol adhesion 'water. These estimates were made by comparing the diata from equilibrium hydration experiments and vacuumfreeze-drying e:wperiments. It thus follows that yform crystals are anhydrate and the X-ray amorphous form exists in either the hydrous or anhydrous form.