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首页> 外文期刊>Crystal growth & design >Physical Stability Enhancement and Pharmacokinetics of a Lithium Ionic Cocrystal with Glucose
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Physical Stability Enhancement and Pharmacokinetics of a Lithium Ionic Cocrystal with Glucose

机译：葡萄糖与锂离子共晶体的物理稳定性增强和药代动力学

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Current lithium drugs are plagued with a narrow therapeutic window and tend to be hygroscopic. However, they remain the gold standard for treating manic episodes in bipolar disorder. In this contribution, we report a crystal engineering study aimed at the preparation and characterization of ionic cocrystals (ICCs) of lithium chloride (LIC) and lithium bromide (LIB) with glucose (GLU). The structure of LIBGLU was studied by single-crystal X-ray diffraction and found to be isostructural with related sodium chloride?glucose ICCs. The physical stability of LICGLU was compared to that of LIC at 50% RH and 25 °C and through dynamic vapor sorption analysis. The blood and brain pharmacokinetics of LICGLU were compared to those of LIC in rat models and revealed little change in performance. This study reveals that ICCs can modestly improve the solid-form stability of lithium salts without impacting in vivo performance, a step toward enabling the development of the next generation of lithium therapeutics.
机译：当前的锂药物困扰于狭窄的治疗窗口并且趋于吸湿。然而，它们仍然是治疗躁郁症躁狂发作的金标准。在这项贡献中，我们报告了一项晶体工程研究，旨在制备和表征氯化锂（LIC）和溴化锂（LIB）与葡萄糖（GLU）的离子共晶体（ICC）。通过单晶X射线衍射研究了LIBGLU的结构，发现其与相关的氯化钠-葡萄糖ICC是同构的。通过动态蒸气吸附分析，将LICGLU与LIC在50％RH和25°C下的物理稳定性进行了比较。在大鼠模型中，LICGLU的血液和脑部药代动力学与LIC进行了比较，显示性能几乎没有变化。这项研究表明，ICC可以适度改善锂盐的固态稳定性，而不会影响体内性能，这是实现下一代锂治疗剂开发的一步。

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