Brusač Edvin, Jeličić Mario-Livio, 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, Marulićev trg 19, 10000 Zagreb, Croatia.
Pharmaceuticals (Basel). 2021 Mar 17;14(3):274. doi: 10.3390/ph14030274.
In this work, a systematical compatibility investigation of 6-mercaptopurine and folic acid, two commonly used medications in the treatment of inflammatory bowel disease, for the needs of a fixed-dose combination development strategy is shown. Various techniques and approaches, such as differential scanning calorimetry, isothermal stress testing, attenuated total reflectance-Fourier-transform infrared spectroscopy, dissolution medium stability and forced degradation studies, were used to elucidate the possible interactions from different aspects. The results predominantly point to the absence of physicochemical interactions between the examined substances in a variety of possible conditions. However, the forced degradation of the blend of substances and excipients in basic conditions showed a drastic degradation of 6-mercaptopurine, signifying that attention needs to be directed to the careful selection of the excipients for the formulation. To sum up, our findings indicate that a fixed-dose combination of 6-mercaptopurine and folic acid could be produced using one formulation blend, immensely simplifying its manufacture.
在这项工作中，展示了针对固定剂量复方开发策略的需求，对6-巯基嘌呤和叶酸这两种治疗炎症性肠病的常用药物进行的系统配伍性研究。采用了各种技术和方法，如差示扫描量热法、等温应力测试、衰减全反射傅里叶变换红外光谱法、溶出介质稳定性和强制降解研究，从不同方面阐明可能的相互作用。结果主要表明，在所研究的各种可能条件下，所检测的物质之间不存在物理化学相互作用。然而，物质与辅料混合物在碱性条件下的强制降解显示6-巯基嘌呤有剧烈降解，这表明在制剂辅料的精心选择上需要加以关注。总之，我们的研究结果表明，可以使用一种制剂混合物来生产6-巯基嘌呤和叶酸的固定剂量复方，极大地简化了其生产过程。
