Discovery and Characterization of a Transient Bis(dichloromethane) Solvate of Ritonavir: A Pathway to Metastable Form IV

This study introduces a new solid form of the antiviral drug ritonavir, specifically a bis(dichloromethane) solvate. The novel solvate was crystallized from a dichloromethane solution with hexane. The solvent is easily lost from the crystal lattice at room temperature, resulting in a known metastable anhydrate form, ritonavir Form IV. The desolvation process was monitored by powder X-ray diffraction over 6 hours using multiple scans. Indexing, along with unit-cell refinement by Pawley fit, were performed for both the novel ritonavir-bis(dichloromethane) solvate and metastable ritonavir Form IV. The presented desolvation of the novel solvate provides a simplified pathway for the isolation of metastable Form IV.