title: Drug-drug cocrystals of antituberculous 4-aminosalicylic acid: Screening, crystal structures, thermochemical and solubility studies.
abstract: Experimental multistage cocrystal screening of the antituberculous drug 4-aminosalicylic acid (PASA) has been conducted with a number of coformers (pyrazinamide (PYR), nicotinamide (NAM), isonicotinamide (iNAM), isoniazid (INH), caffeine (CAF) and theophylline (TPH)). The crystal structures of 4-aminosalicylic acid cocrystals with isonicotinamide ([PASA+iNAM] (2:1)) and methanol solvate with caffeine ([PASA+CAF+MeOH] (1:1:1)) have been determined by single X-ray diffraction experiments. For the first time for PASA cocrystals it has been found that the structural unit of the [PASA+iNAM] cocrystal (2:1) is formed by 2 types of heterosynthons: acid-pyridine and acid-amide. The desolvation study of the [PASA+CAF+MeOH] cocrystal solvate (1:1:1) has been conducted. The correlation models linking the melting points of the cocrystals with the melting points of the coformers used in this paper have been developed. The thermochemical and solubility properties for all the obtained cocrystals have been studied. Cocrystallization has been shown to lead not only to PASA solubility improving but also to its higher stability against the chemical decomposition.
authors.affiliation: G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, 1, Akademicheskaya St., 153045 Ivanovo, Russia.
authors.forename: Ksenia V
authors.initials: KV
authors.lastname: Drozd
authors.affiliation: G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, 1, Akademicheskaya St., 153045 Ivanovo, Russia.
authors.forename: Alex N
authors.initials: AN
authors.lastname: Manin
authors.affiliation: Institute of General and Inorganic Chemistry, RAS, Leninsky Prosp. 31, 119991 Moscow, Russia.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Churakov
authors.affiliation: G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, 1, Akademicheskaya St., 153045 Ivanovo, Russia. Electronic address: glp@isc-ras.ru.
authors.forename: German L
authors.initials: GL
authors.lastname: Perlovich
mesh_terms: D010131:Aminosalicylic Acid / Q000737:chemistry*; D000995:Antitubercular Agents / Q000737:chemistry*; D002110:Caffeine / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray / Q000379:methods; D004355:Drug Stability; D007538:Isoniazid / Q000737:chemistry; D008958:Models, Molecular; D009536:Niacinamide / Q000737:chemistry; D033362:Powder Diffraction / Q000379:methods; D011718:Pyrazinamide / Q000737:chemistry; D012995:Solubility; D013806:Theophylline / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000995:Antitubercular Agents; D009536:Niacinamide; D011718:Pyrazinamide; D002110:Caffeine; C027681:isonicotinamide; D010131:Aminosalicylic Acid; D013806:Theophylline; D007538:Isoniazid
keywords: 4-Aminosalicylic acid (PubChem CID: 4649); Acetone (PubChem CID: 180); Acetonitrile (PubChem CID: 6342); Caffeine (PubChem CID: 2519); Cocrystal; Crystal structure; Desolvation; Dissolution rate; Ethanol (PubChem CID: 702); Isoniazid (PubChem CID: 3767); Isonicotinamide (PubChem CID: 15074); Melting points; Methanol (PubChem CID: 887); Nicotinamide (PubChem CID: 936); Pyrazinamide (PubChem CID: 1046); Screening; Tetrahydrofuran (PubChem CID: 8028); Theophylline (PubChem CID: 2153)