CrystEngComm (2009), 11, 444

​S. Skovsgaard, A. D. Bond, CrystEngComm, 11, 444-453, 2009.
​Eleven co-crystals of benzoic acid derivatives with N-containing bases have been prepared using the two complementary techniques of solution and solvent-drop grinding. In the situations where different polymorphs were obtained from solution and solvent-drop grinding, the form produced by grinding had a crystal higher density and packing coefficient. All the co-crystals obtained successfully inserted N-base molecules into the carboxylic acid dimers that are formed by benzoic acid, salicylic acid and aspirin. Eight of these crystals exhibited the desired layers where there is a clear demarcation between the hydrogen-bonded regions and the principally hydrophobic inter-layer regions.

CrystEngComm (2009), 11, 470

​S. Karki, T. Friscic, W. Jones, CrystEngComm, 11, 470-481, 2009.
​The formation of co-crystals using molecular building blocks in different stoichiometric ratios, has been investigated using co-crystals composed of the model pharmaceutical component nicotinamide (na) and 10 dicarboxylic acids as co-crystal formers. The authors have determined that mechanochemical approaches can allow the control of co-crystal stoichiometry via modification the stoichiometric ratio of reactants in the reactant mixture. In this way, the control of co-crystal composition using neat or liquid-assisted grinding is suggested to be superior to that achieved using the techniques of co-crystal formation from the liquid phase (solution or melt).

CrystEngComm (2009), 11, 2400

​Y. P. Nizhnik , J. Lu , S. V. Rosokha, J. K. Kochi, CrystEngComm, 11, 2400-2405, 2009.
​4-Nitroquinoline-N-oxide is a carcinogen that is commonly used as a model compound in studies of carcino- and mutagenicity mechanisms. Three polymorphs of the compound have been crystallised from solutions in various organic solvents using either (i) slow cooling or evaporation (form I), (ii) moderate rate of cooling (form II) or (iii) flash cooling (form III). The polymorphs have significantly different morphologies, powder diffraction patterns and IR spectra. Packing patterns of the three polymorphs are discussed.

CrystEngComm (2009), 11, 2536

​E. Nauha, H. Saxell, M. Nissinen, E. Kolehmainen, A. Schäfer, R. Schlecker, CrystEngComm, 11, 2536-2547, 2009.
​Thiophanate-methyl (TM) is a fungicide and wound protectant used in protecting citrus fruits against post-harvest decay. TM has been reported in the literature to have a range of melting points (135-200 °C) which may suggest polymorphic behaviour. This study details the results of a crystal form screen looking for polymorphs and solvates. Two polymorphic forms were found to exist along with fourteen solvates, all of which were characterised by X-ray diffraction as well as a range of spectroscopic techniques. Form I was found to be thermodynamically the most stable, but form II can be accessed by desolvation of various different solvate forms.

CrystEngComm (2009), 11, 1823

​S. Aitipamula, P. S. Chow, R. B. H. Tan, CrystEngComm, 11, 1823-1827, 2009.
​The authors report the discovery of three polymorphs of a pharmaceutical co-crystal involving two APIs, ethenzamide and gentisic acid. This is suggested to be the first example of a polymorphic cocrystal that involves two APIs. All three cocrystal polymorphs show an improved dissolution rate compared to ethenzamide. The area of multi-API cocrystals is relatively unexplored and may have potential relevance in the context of combination drugs for pharmaceutical drug development.

Cryst.Growth Des. (2009), 9, 2220

​M. Viertelhaus, R. Hilfiker, F. Blatter, Cryst. Growth Des., 9, 2220–2228, 2009.
​The syntheses, crystal structures and some physicochemical properties of six piracetam co-crystal are reported. Each of the coformers contained at least one carboxylic acid and hydroxyl group. Although the hydrogen-bonded R22(8) heterosynthon between carboxamide and carboxylic acid groups is known to be a common motif, only one of the co-crystals in this study forms that motif. The large number of potential hydrogen-bonding groups appears to disrupt the common ring dimer with complex 3D hydrogen-bonding patterns being produced.

CrystEngComm (2009), 11, 1133

​C. R. Kaiser, K. C. Pais, M. V. N. de Souza, J. L. Wardell, S. M. S. V. Wardell, E. R. T. Tiekink, CrystEngComm, 11, 1133-1140, 2009.
​A study of the crystal packing in 8 chloroquine derivatives has been undertaken to analyse the effects of additional functional groups to the crystal structure. The imine to pyridine (N-H...N) interaction, which generates supramolecular chains, was seen to be persistent only in the absence of competing hydrogen-bonding groups. When a hydroxyl group was introduced this disrupted the former behaviour and produced 2-D arrays involving O-H...N and N-H...O interactions. The occurrence of phenyl stacking contacts, C-H...Cl and Cl...phenyl interactions is also described.

CrystEngComm (2009), 11, 889

​S. Aitipamula, P. S. Chow, R. B. H. Tan, CrystEngComm, 11, 889-895, 2009.
​Ethenzamide (EA) is a poorly water soluble non-steroidal anti-inflammatory drug with analgesic and antipyretic effects. In this study the authors report co-crystal screening studies of EA with saccharin using both solution crystallisation and solvent-drop grinding. Two polymorphs of a 1:1 co-crystal were obtained through solution crystallisation, but the only product of the grinding experiments was the metastable polymorph. Both polymorphs exhibit an amide-imide ring dimer heterosynthon.

CrystEngComm (2009), 11, 791

​A. Portell, R. Barbas, M. Font-Bardia, P. Dalmases, R. Prohens, C. Puigjaner, CrystEngComm, 11, 791-795, 2009
​Ziprasidone, an antipsychotic agent used in the treatment of schizophrenia, is marketed either as an oral capsule (containing the monohydrate hydrochloride salt of the API) or as an injectable drug (ziprasidone mesylate trihydrate). The drug is poorly soluble in water which adversely effects the bioavailability. This study reports a new salt of ziprasidone (malate salt), which exhibits three different polymorphic crystal forms. One of the polymorphs of the malate salt shows the highest solubility ever reported for ziprasidone (14-fold better than the marketed hydrochloride salt).

Cryst.Growth Des. (2009), 9, 3918

​L. Renou, S. Coste, Y. Cartigny, M.-N. Petit, C. Vincent, J.-M. Schneider, G. Coquerel, Cryst. Growth Des., 9, 3918–3927, 2009.
​The monohydrate and anhydrous crystal forms of the antifungal agent ciclopirox ethanolamine (1:1) are reported. It is determined that, under normal conditions, the dehydration of the 1:1 ciclopirox ethanolamine monohydrate structure leads to a 2:1 ciclopirox ethanolamine form through a destructive mechanism. Under saturated ethanolamine vapour pressure, however, the dehydration/hydration mechanism is reversible for up to two cycles without degradation of the 1:1 compound. The study suggests that under normal conditions the 2:1 ciclopirox ethanolamine form is the most stable.