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.

Crystal structure and physicochemical characterization of ambazone monohydrate, anhydrous, and acetate salt solvate.

The crystal structures of the monohydrate and anhydrous forms of ambazone were determined by single-crystal X-ray diffraction (SC-XRD). Ambazone monohydrate is characterized by an infinite three-dimensional network involving the water molecules, whereas anhydrous ambazone forms a two-dimensional network via hydrogen bonds. The reversible transformation between the monohydrate and anhydrous forms of ambazone was evidenced by thermal analysis, temperature-dependent X-ray powder diffraction and accelerated stability at elevated temperature, and relative humidity (RH). Additionally, a novel ambazone acetate salt solvate form was obtained and its nature was elucidated by SC-XRD. Powder dissolution measurements revealed a substantial solubility and dissolution rate improvement of acetate salt solvated form in water and physiological media compared with ambazone forms. Also, the acetate salt solvate displayed good thermal and solution stability but it transformed to the monohydrate on storage at elevated temperature and RH. Our study shows that despite the requirement for controlled storage conditions, the acetate salt solvated form could be an alternative to ambazone when solubility and bioavailability improvement is critical for the clinical efficacy of the drug product.

Crystal structure of the inclusion complex of beta-cyclodextrin with mefenamic acid from high-resolution synchrotron powder-diffraction data in combination with molecular-mechanics calculations.

The crystal structure of the inclusion complex of beta-cyclo-dextrin with mefenamic acid has been determined from a combination of high-resolution synchrotron powder-diffraction data and molecular-mechanics calculations. A grid search indicates two possible solutions, which are corroborated by molecular-mechanics calculations, while Rietveld-refinement results suggest the crystal structure that is more likely to be formed in the solid state. Mefenamic acid is partially included in beta-cyclodextrin with either the xylyl or the benzoic-acid moiety being inside its cavity. In both solutions mefenamic acid and beta-cyclodextrin form a monomeric complex in a herringbone packing scheme.