Nechipadappu, S.K.Tekuri, V.Trivedi, D.R.2026-02-052017Journal of Pharmaceutical Sciences, 2017, 106, 5, pp. 1384-1390223549https://doi.org/10.1016/j.xphs.2017.01.033https://idr.nitk.ac.in/handle/123456789/25639Two novel pharmaceutical co-crystals of anti-inflammatory drug flufenamic acid (FFA) with 2-chloro-4-nitrobenzoic acid (CNB) and ethenzamide (ETZ) have been synthesized by solvent evaporation method as well as by solvent drop-assisted grinding method. The synthesized co-crystals were characterized thoroughly by various spectroscopic methods and crystal structures were determined by single-crystal x-ray diffraction technique. In FFA-CNB co-crystal, robust supramolecular acid-acid homosynthon was observed. FFA-ETZ co-crystal is formed via robust supramolecular acid-amide heterosynthon. In FTIR spectra, a significant shift in the carbonyl stretching frequency was observed for the co-crystals due to the presence of intermolecular hydrogen bond. 1H nuclear magnetic resonance study suggests the presence of hydrogen bond in the solution state of FFA-ETZ co-crystal; however, it was absent for FFA-CNB co-crystal. Solubility study in Millipore water revealed that the solubility of FFA is increased by 2-fold when it is in the form of FFA-CNB co-crystal and no increment in the solubility of FFA was observed in FFA-ETZ co-crystal. About 5-fold increment in the solubility of FFA was observed in both the co-crystals in 0.1 N HCl (pH 1) solution. The synthesized co-crystals were found to be non-hygroscopic at ?75% relative humidity and stable for a period of 6 months at ambient temperature (?25°C). © 2017 American Pharmacists Association®2 chloro 4 nitrobenzoic acidethenzamideflufenamic acidhalogenhydrogennitrobenzoic acid derivativeunclassified drugantiinflammatory agentArticlecrystalcrystal structuredifferential scanning calorimetrydilutiondrug solubilityenvironmental temperatureevaporationhumidityhydrogen bondinfrared spectroscopylow temperaturemelting pointpHproton nuclear magnetic resonanceroom temperaturesynthesistemperature sensitivitythermal analysiswettabilityX ray diffractioncrystallizationdrug combinationproceduresAnti-Inflammatory AgentsCrystallizationDrug CombinationsFlufenamic AcidX-Ray Diffraction