Ethenzamide (CAS: 938-73-8, 2-ethoxybenzamide, ETZ) is a non-steroidal anti-inflammatory drug with analgesic and antipyretic effects[1]. It can be used to treat mild to moderate pain in muscle, bone and joint diseases. ETZ belongs to class II of Biological drug Classification System (BCS), and its main disadvantages are poor solubility and low bioavailability[2]. The structures of cocrystal of ETZ have been published and deposited in CSD (Cambridge Structural Database), which was obtained with furosemide (CCDC:2114160, SARQOV)[3], sinapic acid (CCDC:1581650, DEYQUW)[4], 2,5-dihydroxybenzoic acid (CCDC:1522933, FENQEX), 3,4-dihydroxybenzoic acid (CCDC:1522937, FENRIC)[5], phenol (CCDC:1879336, VUKSEC)[6], 3,5-dinitrobenzoic acid (CCDC:752467, WUZHOP)[7], 2,4-dihydroxybenzoic acid (CCDC:1825011, JIFHAK)[8], 3,4,5-trihydroxybenzoic acid (CCDC:1468148, ORIKIL), 2-nitrobenzoic acid (CCDC:1468153, ORIKOR), 3-nitrobenzoic acid (CCDC:1468154, ORIKUX), 2,4-dinitrobenzoic acid (CCDC:1468159, ORILAE), 3-methylbenzoic acid (CCDC:1468161, ORILEI)[9], 2-hydroxybenzoic acid (CCDC:752480, REHSAA)[10], pentanedioic acid (CCDC:1854255, TIWPIB)[11], (2Z)-but-2-enedioic acid (CCDC:1854256, TIWPOH)[11], Flufenamic Acid (CCDC:1448786, FAQXAZ)[12], Ferulic acid (CCDC:1448786, FAQXAZ)[13], propanedioic acid (CCDC:1854257, TIWPUN)[14], ethylmalonic acid (CCDC:752465, VAKTOS)[15], Saccharin (CCDC:711674, VUHFIO)[16]and so on.
Different coformers can cause different trend of solubilities. For example, ETZ·3,5-dinitrobenzoic acid (19.47 mg·mL− 1), ETZ·2,4-dihydroxybenzoic acid (4.78 mg·mL− 1) improved the solubility of ETZ (1.45 mg·mL− 1), while ETZ·ferulic acid (1.15 mg·mL− 1) reduced the solubility of ETZ (1.45 mg·mL− 1). In this research, we discovered the cocrystal of ETZ·2TMA·MeOH, which laid a foundation for the further study of ETZ new cocrystal.