First‐line antituberculosis drug, pyrazinamide, its pharmaceutically relevant cocrystals and a salt. Issue 5 (5th October 2017)

• Record Type: Journal Article
• Authors: Sarmah, Kashyap Kumar; Rajbongshi, Trishna; Bhowmick, Sourav; Thakuria, Ranjit
• Is Part Of: Acta crystallographica. Volume 73:Issue 5(2017:Oct.)
• Page Start: 1007
• Page End: 1016
• Publication Date: 2017-10-05
• Subjects: molecular salt -- nutraceutical -- pharmaceutical cocrystal -- supramolecular synthon
• DOI: 10.1107/S2052520617011477
• Languages: English
• ISSNs: 2052-5206

Abstract

Abstract : Pharmaceutical cocrystals of the antituberculosis drug pyrazinamide with substituted hydroxyacids (2, 4‐dihydroxybenzoic acid; 2, 6‐dihydroxybenzoic acid; 3, 5‐dihydroxybenzoic acid and ferulic acid) and a molecular salt with p ‐toluenesulfonic acid have been synthesized using both mechanical grinding as well as solution crystallization. This is the first report of the pyrazinamide salt. Abstract : 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 with p ‐toluenesulfonic acid ( p TSA) 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 + · p TSA − > Pyz·35DHBA > Pyz > Pyz·26DHBA > Pyz·24DHBA > Pyz·FRA. A twofold enhancement in solubility of Pyz + · p TSA − molecular salt compared with the parent drug suggests a potential drug formulation for the treatment of tuberculosis.