Ngilirabanga Jean Baptiste, Aucamp Marique, Pires Rosa Paulo, Samsodien Halima
School of Pharmacy, University of the Western Cape, Cape Town, South Africa.
Faculty of Pharmaceutical Sciences, State University of Campinas, Saö Paulo, Brazil.
Front Chem. 2020 Nov 16;8:595908. doi: 10.3389/fchem.2020.595908. eCollection 2020.
The present work reports two novel pharmaceutical co-crystals; 2:1 isoniazid-glutaric acid (INHGA) and 2:1 pyrazinamide-glutaric acid (PGA). Isoniazid and pyrazinamide are key first-line drugs used for the treatment of tuberculosis. The co-crystals were produced solid-state and solvent assisted grinding methods. Thermal characteristics of the samples were obtained using the differential scanning calorimetry, hot stage microscopy, and thermogravimetric analyses. The morphology of the powder samples by scanning electron microscopy, structural analysis by Fourier transform infrared spectroscopy and powder X-rays diffraction ensured co-crystal formation. Thermal analyses confirmed the co-crystals with new melting transitions ranging between their respective starting materials. Unique morphologies of the co-crystal particles were clear in SEM micrographs. The formation of intermolecular interactions with the co-crystal former was confirmed by the FT-IR spectral band shifting and was supported by distinct PXRD patterns of co-crystals thereby authenticating the successful co-crystal formation. solubility evaluation of the synthesized co-crystals by HPLC suggested a remarkable increase in solubility of both INH and PZA in their respective co-crystals.
2:1异烟肼 - 戊二酸（INHGA）和2:1吡嗪酰胺 - 戊二酸（PGA）。异烟肼和吡嗪酰胺是用于治疗结核病的关键一线药物。共晶体通过固态和溶剂辅助研磨法制备。使用差示扫描量热法、热台显微镜和热重分析获得样品的热特性。通过扫描电子显微镜观察粉末样品的形态，利用傅里叶变换红外光谱和粉末X射线衍射进行结构分析，确定了共晶体的形成。热分析证实了共晶体具有介于各自起始原料之间的新的熔融转变。在扫描电子显微镜图像中，共晶体颗粒具有独特的形态。傅里叶变换红外光谱带的移动证实了与共晶体形成剂之间分子间相互作用的形成，并且共晶体独特的粉末X射线衍射图谱也支持了这一点，从而证实了共晶体的成功形成。通过高效液相色谱法对合成的共晶体进行溶解度评估表明，异烟肼（INH）和吡嗪酰胺（PZA）在各自的共晶体中的溶解度均显著增加。
