Desolvation Behavior of Indinavir Sulfate Ethanol and Follow-Up by Terahertz Spectroscopy

Int J Pharm. 2019 Aug 15;567:118446. doi: 10.1016/j.ijpharm.2019.06.037. Epub 2019 Jun 18.


Active pharmaceutical ingredients are composed of single-component or multicomponent crystals. Multicomponent crystals include salts, co-crystals, and solvates. Indinavir sulfate is the ethanol solvate form of indinavir that is known to deliquesce through moisture absorption. However, the detailed behavior of solvent molecules in the crystal has not been investigated. In this study, we studied the desolvation mechanism of indinavir sulfate ethanol and investigated the behavior of solvent molecules in the solid from. Indinavir sulfate ethanol contained 1.7 molecules of ethanol, 0.7 of which desolvated at room temperature. They were originally two ethanol solvent molecules; one molecule of ethanol desolvated at room temperature, and the conformation of the remaining ethanol and t-butyl groups changed in conjunction with the removal of one ethanol molecule. Desolvation could hardly be detected by powder X-ray diffraction; however, it was detected using terahertz spectroscopy. Terahertz measurement of desolvation showed a high correlation with thermogravimetry data, suggesting that desolvation could be observed non-destructively using terahertz spectroscopy. We concluded that indinavir sulfate 1 ethanol deliquesced at 60% relative humidity, and it turned into an amorphous solid after drying.

Keywords: Crixivan; Crystal structure; Desolvation; Indinavir sulfate ethanol; Solvate; Terahertz spectroscopy.

MeSH terms

  • Desiccation
  • Ethanol / chemistry*
  • Humidity
  • Indinavir / chemistry*
  • Powder Diffraction
  • Solvents / chemistry*
  • Terahertz Spectroscopy
  • X-Ray Diffraction


  • Solvents
  • Ethanol
  • Indinavir