Sarraguça Mafalda C, Ribeiro Paulo R S, Santos Adenilson O, Silva Marta C D, Lopes João A
REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal.
Centro de Ciências Sociais, Saúde e Tecnologia, Universidade Federal do Maranhão, Imperatriz, MA, Brazil.
Int J Pharm. 2014 Aug 25;471(1-2):478-84. doi: 10.1016/j.ijpharm.2014.06.003. Epub 2014 Jun 4.
Cocrystals represent a class of crystalline solids consisting of two or more molecular species usually held together by non-covalent bonds. Pharmaceutical cocrystals can alter the physicochemical properties of the active pharmaceutical ingredient to improve solubility, dissolution rate, particle properties and stability. This work presents a process analytical technology (PAT) approach to monitor on-line the cocrystallization of furosemide and adenine by solvent evaporation using near infrared spectroscopy (NIRS). Furosemide and adenine were added to a small volume of methanol in a beaker and stirred on an orbital stirring table during 8h at room temperature. The on-line monitoring was performed with a FT-NIR spectrometer fitted with a reflectance fiber optic probe. Monitoring was performed with the probe tip placed 1cm above the cocrystallization medium to avoid interference with the cocrystallization process. Cocrystals were vacuum dried to remove residual solvent and characterized off-line by NIRS, MIRS, DSC and XRPD. Results demonstrate that it was possible to follow the main cocrystallization events on-line.
共晶体是一类晶体固体，由两种或更多分子物种组成，通常通过非共价键结合在一起。药物共晶体可以改变活性药物成分的物理化学性质，以提高溶解度、溶解速率、颗粒性质和稳定性。这项工作提出了一种过程分析技术（PAT）方法，通过近红外光谱（NIRS）在线监测呋塞米和腺嘌呤通过溶剂蒸发的共结晶过程。将呋塞米和腺嘌呤加入到烧杯中的少量甲醇中，并在室温下于轨道搅拌台上搅拌8小时。使用配备反射光纤探头的傅里叶变换近红外光谱仪进行在线监测。监测时将探头尖端放置在共结晶介质上方1厘米处，以避免干扰共结晶过程。共晶体经真空干燥以除去残留溶剂，并通过NIRS、MIRS、DSC和XRPD进行离线表征。结果表明，可以在线跟踪主要的共结晶事件。
