Crystal Structure and Desolvation Behaviour of the Tadalafil Monosolvates with Acetone and Methyl Ethyl Ketone

Crystal structures of Tadalafil (TDF) monosolvated forms with acetone (ACE) and methyl ethyl ketone (MEK) were determined by single-crystal X-ray diffraction in which same persistent chains of TDF molecules are present as in the reported structures. The solvates crystallize in a higher orthorhombic symmetry than the known forms with monoclinic structures. Weak interactions between TDF and solvent molecules are present in both solvates, leading to slight conformational distortions of TDF molecules. The MEK solvate showed slightly higher stability than the ACE solvate, regardless of their highly similar molecular conformations and crystal packing. Desolvation into anhydrous TDF was achieved by heating, exposure to temperature and relative humidity and by mechanical stress. The high solubility of TDF in ACE and MEK solvents combined with the ease of desolvation of the resulting solvated forms indicates the viability of the solvates use as intermediates in the TDF crystallization process. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3782-3788, 2015