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 |
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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. |
doi_str_mv | 10.1021/cg501310d |
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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.</description><subject>Cross-disciplinary physics: materials science; rheology</subject><subject>Exact sciences and technology</subject><subject>Materials science</subject><subject>Methods of crystal growth; physics of crystal growth</subject><subject>Physics</subject><issn>1528-7483</issn><issn>1528-7505</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNptkMtKA0EQRRtRMEYX_kFvXLgYre6e51JCjIGAAXUpQ_XL6TiP0D1B5u8zEo0bV1UUtw6cS8g1gzsGnN2rjwSYYKBPyIQlPI-yBJLT3z3OxTm5CGEDAFkqxIS8r6shOIU1felRutr1A523FbbKNKbtKbaariv0Daru07WmdyrQzlKkK9dXbtfQZdc6RWed8kPoR87XeKeLeqe6YC7JmcU6mKufOSVvj_PX2VO0el4sZw-rCHle9JGOgQNYq1OZCsul1tIUPJYZz3NWcChkjkViJBSIMs8EpIlgWvPMCLAohZiS2wNX-S4Eb2y59a5BP5QMyu9eymMvY_bmkN1iGL2tH11dOD7wAmKWcfjLoQrlptv5djT4h7cHg11vBQ</recordid><startdate>20141105</startdate><enddate>20141105</enddate><creator>Duggirala, Naga Kiran</creator><creator>Smith, Adam J</creator><creator>Wojtas, Łukasz</creator><creator>Shytle, R. 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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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