Physical Stability Enhancement and Pharmacokinetics of a Lithium Ionic Cocrystal with Glucose
Physical Stability Enhancement and Pharmacokinetics of a Lithium Ionic Cocrystal with Glucose
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DOI：
10.1021/cg501310d
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发表时间：
2014-11-01
影响因子：
3.8
通讯作者：
Zaworotko, Michael J.
中科院分区：
文献类型：
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作者：
Duggirala, Naga Kiran;Smith, Adam J.;Zaworotko, Michael J.
目前的锂药物存在治疗窗口狭窄和吸湿性的问题。然而，它们仍然是治疗双相情感障碍躁狂发作的黄金标准。在这篇文章中，我们报道了一项晶体工程研究，旨在制备和表征葡萄糖（GLU）的氯化锂（LIC）和溴化锂（LIB）离子共晶（ICCs）。用单晶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具有相同的结构。通过动态蒸汽吸附分析，比较了LICGLU与LIC在50% RH和25℃条件下的物理稳定性。将LICGLU与LIC在大鼠模型中的血药代动力学和脑药代动力学进行比较，结果显示LICGLU对大鼠的性能变化不大。这项研究表明，ICCs可以适度改善锂盐的固体形态稳定性，而不会影响体内性能，这是实现下一代锂疗法开发的一步。
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 chlorideglucose ICCs. The physical stability of LICGLU was compared to that of LIC at 50% RH and 25 degrees 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.