Hydrochlorothiazide (HCT) is a diuretic drug used for the treatment of hypertension andedemas, while pyrazinamide (PZA) is one of the most important front-line medicines for tuberculosis. Both drugs suffer from low solubility.The low bioavailability is partially attributed to itspoor aqueous solubility.Pharmaceutical co-crystal approach has been used to alter the solid-state properties of a drug substance, particularly its solubility and bioavailability.

Due to the advent of supramolecular synthesis, co-crystals canbe designed rationally utilizing the basic concepts of crystals engineering. Therefore, for strategic co-crystal formation, it is critical to deeply understand the non-covalent contacts in the pharmaceutical co-crystals. The ease of preparation and the availability of various co-formers offer new opportunities for pharmaceutical co-crystals to have a broad prospect in becoming a solid form suitable for formulations in pharmaceutical development.

In this work, a series of co-crystals were designed and synthesized.The HCT-PZA co-crystal is a drug-drug co-crystal which is classified as a subset of pharmaceuticalco-crystals andcan be used as candidates for development of combinationdrug products or fixed dose combinations.The HCT co-crystals reported in this work represent unique solid modifications and display obviously different physical and chemical properties comparing with their parent compounds. Particularly, the HCT-PZA co-crystal is a promising candidate for improving the solubility and dissolution rate of HCT.

This work has been published on the CrystEngComm.Full text:http://pubs.rsc.org/en/content/articlepdf/2014/CE/C4CE00666F

Formation of HCT-PZA drug-drug co-crystal

“honeycomb” pattern