ArticleScientific reports2025
Effect of solvent evaporation on the liquid-crystalline order of itraconazole.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Solvent evaporation is widely used for the formation of amorphous active pharmaceutical ingredients. This study investigates the effect of solvent evaporation on the structure of itraconazole - an antifungal drug and a model thermotropic liquid crystal that exhibits nematic and smectic phases when supercooled from the melt, and when cooled below the glass transition temperature at ~ 330 K, it forms glass with frozen liquid-crystalline order. Using X-ray scattering, it is demonstrated that the solid form of itraconazole obtained at room temperature via evaporation of dichloromethane reveals a smectic order extending up to ~ 15 nm, which is about two times more than what is observed for itraconazole glass obtained by the conventional vitrification. Moreover, the degree of the smectic order may be tuned by adjusting the concentration of the drug in the solution or the choice of solvent. The obtained results are in agreement with previous reports, which indicated an enhancement of smectic order in the system of itraconazole with glycerol derived by evaporation from dichloromethane as compared to pure itraconazole glass [Fatina, C. et al. (2024). Cryst. Growth & Des., 24(11), 4596-4603]. Nevertheless, the new insight has clearly shown that glycerol stabilizing the liquid-crystalline order in itraconazole is not required at all for its generation. This can be achieved with pure itraconazole by evaporation of solvent. Moreover, the presence of glycerol does not extend the long-term room temperature physical stability of the smectic structure in itraconazole. Our findings may be used for producing non-crystalline formulations offering improvements in drug release over the conventional crystalline form.
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