Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India.
Pharmaceutical Chemistry Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, U.P., India.
J Pharm Sci. 2024 Mar;113(3):647-658. doi: 10.1016/j.xphs.2023.07.001. Epub 2023 Aug 16.
Dimethyl fumarate (DMF) is an FDA-approved drug for treating relapsing-remitting multiple sclerosis; but it is susceptible to sublimation leading to its loss during processing. Cocrystals can protect against thermal energy via the interaction of DMF with a coformer via weak forces of interaction. With this hypothesis, we have, for the first time, prepared DMF cocrystals using the solvent evaporation method using coformers like citric acid and succinic acid screened by in-silico predictions and hydrogen bonding properties. Analysis using infra-red (IR), powder x-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and sublimation evaluation characterized cocrystals and their thermostability. Comparative analysis of the release profile has been done by dissolution and pharmacokinetic study of DMF and its cocrystals. The cocrystals have improved thermal stability and better pharmacological activities than DMF. In the safety and efficacy evaluation of the formulated cocrystals, they were found to be non-cytotoxic, antioxidant, and inhibiting IL-6 and TNF-α in PBMC induced by lipopolysaccharide (LPS). We have obtained cocrystals of DMF with improved thermal stability and better pharmacological activities than DMF.
富马酸二甲酯（DMF）是一种经美国食品和药物管理局批准用于治疗复发缓解型多发性硬化症的药物；但它易升华，在加工过程中会导致其损失。共晶可以通过 DMF 与共晶形成物之间的弱相互作用来保护热能。基于这一假设，我们首次使用溶剂蒸发法，使用通过计算机预测和氢键特性筛选出的共晶形成物，如柠檬酸和琥珀酸，制备了 DMF 共晶。使用红外（IR）、粉末 X 射线衍射（PXRD）、热重分析（TGA）、差示扫描量热法（DSC）和升华评估对共晶及其热稳定性进行了分析。通过 DMF 及其共晶的溶解和药代动力学研究对释放曲线进行了比较分析。与 DMF 相比，共晶具有更好的热稳定性和更好的药理活性。在配方共晶的安全性和疗效评估中，发现它们无细胞毒性、抗氧化，并且可以抑制脂多糖（LPS）诱导的 PBMC 中 IL-6 和 TNF-α 的产生。我们已经获得了具有改善的热稳定性和更好的药理活性的 DMF 共晶。
