Solid state characterisation of four solvates of R-cinacalcet hydrochloride

The study describes the solid state behaviour, and the thermal and structural features of four monosolvates of cinacalcet hydrochloride with acetic acid, chloroform, 1,4-dioxane, and tetrachloromethane, and summarises the transformation and production pathways of the seven crystal forms of this promising drug compound (calcimimetic). The solvates were identified and characterised by hot-stage microscopy, differential scanning calorimetry, thermogravimetric analysis, FT-infrared and Raman spectroscopy, powder diffractometry, and the structure of the acetic acid solvate was determined by single crystal X-ray diffraction. All solvates are unstable when removed from the mother liquor and desolvate to form II. To our knowledge, phase pure samples of this metastable but kinetically stable form are only obtainable via desolvation of one of the solvates. Thermoanalytical data and a conformation and packing analysis of the acetic acid solvate and the polymorphs indicate that the desolvation is a destructive process forming an isotropic intermediate state with high molecular mobility. Therefore the desolvation process results in the kinetic form II, which is structurally less similar to the solvate than the thermodynamically stable form III degrees. The study demonstrates that in spite of strong structural similarities between a solvate and a polymorph we can obtain a polymorph with less structural resemblance to the solvent adduct if the structure collapses during the desolvation process.