Jeličić Mario-Livio, Brusač Edvin, Kurajica Stanislav, Cvetnić Matija, Amidžić Klarić Daniela, Nigović Biljana, Mornar Ana
Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia.
Faculty of Chemical Engineering and Technology, University of Zagreb, Marulić Square 19, 10000 Zagreb, Croatia.
Pharmaceutics. 2021 Mar 17;13(3):400. doi: 10.3390/pharmaceutics13030400.
The simultaneous administration of sulfasalazine and folic acid is regular practice in the therapy of inflammatory bowel diseases in order to maintain sufficient folate concentration in patients. Having multiple drugs in the therapy increases the possibility of patients failing adherence, thus unintentionally endangering their health. A fixed-dose combination of sulfasalazine and folic would simplify the classical polytherapeutic approach; however, the physicochemical compatibility investigation of two active pharmaceutical ingredients plays an important role in the development of such a product. In this work, various analytical tools were used to determine the physicochemical compatibility of sulfasalazine and folic acid. For the evaluation of chemical compatibility, infrared spectroscopy in combination with advanced statistical methods, such as the principal component analysis and cluster analysis, were used, whilst a simultaneous thermogravimetry/differential thermal analysis gave us an insight into the physical compatibility of two drugs. Isothermal stress testing, forced degradation and dissolution studies, followed by the analysis with a developed chromatographic method for the monitoring of folic acid, sulfasalazine and two of its related impurities, sulfapyridine and salicylic acid, gave us an insight into its chemical compatibility. The combination of the results obtained from the used techniques implies a satisfactory physicochemical compatibility between sulfasalazine and folic acid, which opens the path to the development of the proposed fixed-dose combination.
在炎症性肠病的治疗中，同时给予柳氮磺胺吡啶和叶酸是常规做法，目的是维持患者体内足够的叶酸浓度。治疗中使用多种药物增加了患者不依从的可能性，从而无意中危及他们的健康。柳氮磺胺吡啶和叶酸的固定剂量组合将简化传统的多药治疗方法；然而，两种活性药物成分的物理化学相容性研究在此类产品的开发中起着重要作用。在这项工作中，使用了各种分析工具来确定柳氮磺胺吡啶和叶酸的物理化学相容性。为了评估化学相容性，使用了红外光谱结合主成分分析和聚类分析等先进统计方法，同时热重/差示热分析让我们深入了解了两种药物的物理相容性。等温应力测试、强制降解和溶出度研究，随后用一种开发的色谱方法分析以监测叶酸、柳氮磺胺吡啶及其两种相关杂质磺胺吡啶和水杨酸，让我们深入了解了其化学相容性。从所使用技术获得的结果表明柳氮磺胺吡啶和叶酸之间具有令人满意的物理化学相容性，这为所提议的固定剂量组合的开发开辟了道路。
