Spironolactone saccharin 1:1 cocrystal | 1227053-78-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: Spironolactone saccharin 1:1 cocrystal
• 英文别名: S-[(7R,8R,9S,10R,13S,14S,17R)-10,13-dimethyl-3,5'-dioxospiro[2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-17,2'-oxolane]-7-yl] ethanethioate;1,1-dioxo-1,2-benzothiazol-3-one
• CAS: 1227053-78-2
• 化学式: C₇H₅NO₃S*C₂₄H₃₂O₄S
• 分子量: 599.769
• InChiKey: MYDOEFYQWSUXMF-FXFKJASFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.97
• 重原子数：
  41
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  157
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  生成 Spironolactone saccharin 1:1 cocrystal
  参考文献：
  名称：

  A Spironolactone−Saccharin 1:1 Cocrystal Hemihydrate

  摘要：

  We investigated the structures Of the hydrated and dehydrated states and the in vitro dissolution of a spironolactone saccharin 1:1 cocrystal hemihydrate, the cocrystal hydrate of a nonionizable, poorly water-soluble drug with a pharmaceutically acceptable coformer. The cocrystal hydrate has linear channels in its crystal structure where the water molecules locate and shows nonstoichiometric hydration, suggesting that the cocrystal hydrate and anhydrate are isostructural. Single-crystal X-ray diffraction using the cocrystal anhydrate prepared from single-crystal to single-crystal dehydration confirmed the isostructural relationship and showed retention of the linear channels and subtle shrinkage of the unit cell volume (similar to 0.3%) after dehydration. The dissolution of the cocrystal hydrate was evaluated in simulated intestinal fluid and fasted-state simulated intestinal fluid. The cocrystal hydrate improved solubility at about 2-fold the maximum supersaturated concentration with respect to the saturated solubility of spironolactone form II (the most stable form) in both media. However, the concentration decreased after reaching the maximum and the cocrystal hydrate converted to a previously unreported spironolactone 1/3 hydrate which was similar to 0.8 times less soluble than spironolactone form II.

  DOI：

  10.1021/cg901242q