The co-crystals of three industrially important pharmaceutical molecules, the Vitamin B group member nicotinamide (1), the antihyperlipidemic drug clofibric acid (2), and the nonsteroidal anti-inflammatory drug diclofenac (3), are synthesized with the co-crystal former isonicotinamide and characterized by thermal analysis and single crystal X-ray diffraction. Two dimorphic hydrates of isonicotinamide were obtained during the course of these experiments: hydrate 4 (form I) has been reported recently, and hydrate 5 (form II) is new. Both are monohydrates but differ in the number of independent molecules in the asymmetric unit, Z 0 =2 and 8, respectively. Form II is metastable compared to I and converts to form I in the solid state. In all three pharmaceutical co-crystals, it is the pyridine N atom of either the nicotinamide molecule in 1 or the N atom of the isonicotinamide molecule in 2 and 3 that is used in connecting the different molecules together, as a hydrogen bond acceptor from the amine of the isonicotinamide in 1 and the carboxylic acid protons in 2 and 3. The carboxylic acid 3 3 3 pyridine hydrogen bond is an often used supramolecular synthon. A survey of relevant structures in the Cambridge Structural Database of isonicotinamide and nicotinamide co-crystals is given for completeness, and the co-crystal former ability of isonicotinamide and nicotinamide was investigated by performing density functional theory calculations.

The relationships between the melting point, solubility and structure was investigated in a series of multicomponent crystals of fumaric and adipic acid.

The two polymorphic forms R and β of the active pharmaceutical ingredient 2- [4-[2-(4-chlorobenzamide)ethyl]phenoxy]-2-methylpropanoic acid (bezafibrate) have been reinvestigated and fully characterized by optical microscopy, infrared spectroscopy, differential scanning calorimetry, thermal gravimetric analysis, variable temperature X-ray powder diffraction, and single crystal X-ray diffraction. Form R is obtained from ethanol, whereas form β can be grown from a 2-butanone solution provided that stoichiometric quantities of iso-nicotinamide are present. Without iso-nicotinamide, both forms grow concomitantly from a 2-butanone solution. The two forms are related enantiotropically, with form β converting to form R at 160.7 °C. Form β is the more stable form at room temperature and at temperatures below the transition temperature of 160.7 °C. The two polymorphs arise from conformational differences which result in vastly different hydrogen bonding interactions and subsequent crystal packing in the solid state. The crystal habits of the two forms reflect the different solid-state packing observed by single crystal X-ray diffraction. Computational modelling calculations on the energy of the conformations have been carried out in the solid state and compared to those energy minima calculated in the gas phase.