The first example of a trimorphic cocrystal involving two active pharmaceutical ingredients, ethenzamide and gentisic acid, is reported; metastable polymorphs convert to the stable form upon solid-state grinding; pharmaceutical cocrystals involving two or more APIs have potential relevance to combination drugs.

Novel cocrystals of an anti-tuberculosis drug, Isoniazid (INH), with pharmaceutically acceptable coformers such as nicotinamide (NA), 4-hydroxybenzoic acid (HBA), fumaric acid (FA), and succinic acid (SA) are reported. Cocrystallization experiments involving INH and HBA produced two polymorphs of a novel hydrate of the INH·HBA cocrystal. Similarly, cocrystallization of INH and FA produced a novel polymorph of the reported INH·FA cocrystal. We have successfully explored the idea of designing ternary cocrystals involving INH with NA and FA or SA. All the novel solids were thoroughly characterized and their crystal structures determined. All the crystal structures feature an acid–pyridine heterosynthon involving INH and the carboxylic acid. Stability of the novel cocrystals was evaluated by slurry experiments and dynamic vapor sorption studies. In addition, stability of the cocrystals at accelerated test conditions (40 °C, 75% RH) was also tested. Anhydrous INH·HBA cocrystal and Form I of INH·HBA cocrystal hydrate were found to convert to Form II of the INH·HBA hydrate, and Form II of INH·FA cocrystal converted to Form I of the INH·FA cocrystal. Ternary cocrystals remain stable at all test conditions. Solubility and dissolution experiments revealed a greater solubility of the INH·NA·SA cocrystal and its dissolution rate is comparable to the dissolution rate of the native INH. All other cocrystals showed lower solubility and dissolution rate compared to INH.

Pharmaceutical co-crystallizing ability of an antibiotic agent, nitrofurantoin, is screened with three isomeric monohydroxybenzoic acids. 1 : 1 co-crystal of nitrofurantoin-4-hydroxybenzoic acid has been prepared and structurally characterized. Further, the co-crystal displays superior physicochemical and photo-stability compared to nitrofurantoin.

The importance of relative growth rates in the preponderance of α- over γ-glycine during solution crystallisation has been confirmed. Most surprisingly tailor-made additives drastically accelerated the growth of γ-glycine—an unexpected and key factor in the polymorphic outcome of glycine crystallisation.