Journal
MOLECULAR PHARMACEUTICS
Volume -, Issue -, Pages -Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.2c00122
Keywords
cocrystal solubility; coformer concentration; critical supersaturation; dose number; solution-mediated phase transformation; cocrystal phase diagram
Funding
- Brazilian funding agency Coordination of Improvement of Higher Education Personnel (CAPES)
- Brazilian funding agency National Council for Scientific and Technological Development (CNPq)
- Irish Fulbright Commission
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This study presents a graphical analysis of drug and coformer concentrations contributed by dissolving cocrystals in a simplified cocrystal phase diagram. The conceptual basis and analysis identify parameters that control cocrystal dissolution-drug supersaturation-precipitation behavior. The study demonstrates and quantifies the important effects of coformer concentration, cocrystal dose, and cocrystal solubility on drug supersaturation levels through the DSP index. The findings can be used to guide the addition of coformer to cocrystal dissolution media or formulations.
A graphical analysis of both drug and coformer concentrations contributed by dissolving cocrystals is presented in the context of a simplified cocrystal phase diagram. The conceptual basis and analysis identify parameters that control cocrystal dissolution-drug supersaturation-precipitation (DSP) behavior. The important effects of coformer concentration, cocrystal dose, and cocrystal solubility on drug supersaturation levels are demonstrated and quantified by the DSPindex. While the studies presented rely on high and nonstoichiometric coformer concentrations contributed by the dissolving cocrystals, the concepts and findings can answer the question of whether and how much coformer should be added to cocrystal dissolution media or formulations.
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