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A unique set of carbamazepine (CBZ) non-stoichiometric cocrystal hydrates with 34/35DHBA have been synthesized which are facilitated by their isostructural nature with the CBZ dihydrate, resulting in coformer–water exchange (molecular alloy).

Cocrystallization of the antituberculosis drug pyrazinamide (PZA) with several substituted aromatic carboxylic acids as coformers was studied. The combinations were analyzed by X-ray diffraction and melting behavior to assess the formation of eutectic versus cocrystal. Benzoic acid, cinnamic acid, and N-heterocycle coformers gave eutectics, whereas the majority of their hydroxyl/methoxy substitutes formed cocrystals with PZA. X-ray crystal structures were obtained for some cocrystals, and binary phase diagrams were constructed to determine eutectic compositions. Differences in functional group position and variations in supramolecular growth were found to dictate the formation of eutectics versus cocrystals. Supramolecular synthon energy calculations on selected combinations validated the formation of eutectic versus cocrystal.

A few pyrazinamide (Pyz) cocrystals involving hydroxybenzoic/cinnamic acid derivatives [2,4-dihydroxybenzoic acid (24DHBA); 2,6-dihydroxybenzoic acid (26DHBA); 3,5-dihydroxybenzoic acid (35DHBA) and nutraceutical molecule ferulic acid (FRA)] and the first example of a molecular salt withp-toluenesulfonic acid (pTSA) have been prepared and characterized using various solid-state techniques. A high-temperature cocrystal polymorph of Pyz·FRA has been characterized from the endothermic peaks observed using differential scanning calorimetry. The presence of substituent groups carrying hydrogen bond donors or acceptors and their influence on supramolecular synthon formation has been investigated using a Cambridge Structural Database search. Equilibrium solubility of all the binary complexes of Pyz follows the order of their coformer solubility,i.e.Pyz+·pTSA−> Pyz·35DHBA > Pyz > Pyz·26DHBA > Pyz·24DHBA > Pyz·FRA. A twofold enhancement in solubility of Pyz+·pTSA−molecular salt compared with the parent drug suggests a potential drug formulation for the treatment of tuberculosis.

Cocrystallization of racemic dl-tartaric acid (dl-ta) and achiral isoniazid (ISN) was investigated using mechanochemistry. Neat grinding (NG) and liquid-assisted grinding (LAG) in the presence of non-polar liquids result in the formation of a conglomerate (ISN·d-ta/ISN·l-ta); whereas LAG with polar liquids yields racemic salt ISN·dl-ta. The effect of solvent polarity and dipole moment in mechanochemistry is discussed.