Physical Stability Enhancement and Pharmacokinetics of a Lithium Ionic Cocrystal with Glucose

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 co...

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Veröffentlicht in:Crystal growth & design 2014-11, Vol.14 (11), p.6135-6142
Hauptverfasser: Duggirala, Naga Kiran, Smith, Adam J, Wojtas, Łukasz, Shytle, R. Douglas, Zaworotko, Michael J
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container_end_page 6142
container_issue 11
container_start_page 6135
container_title Crystal growth & design
container_volume 14
creator Duggirala, Naga Kiran
Smith, Adam J
Wojtas, Łukasz
Shytle, R. Douglas
Zaworotko, Michael J
description 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.
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subjects Cross-disciplinary physics: materials science
rheology
Exact sciences and technology
Materials science
Methods of crystal growth
physics of crystal growth
Physics
title Physical Stability Enhancement and Pharmacokinetics of a Lithium Ionic Cocrystal with Glucose
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