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• W2893056265 abstract "Liquid crystalline (LC) materials and their nonmedical applications have been known for decades, especially in the production of displays; however, the pharmaceutical implications of the LC state are inadequately appreciated, and the misunderstanding of experimental data is leading to possible errors, especially in relation to the physical stability of medicines. The aim of this work was to study LC phases of itraconazole (ITZ), an azole antifungal active molecule, and for the first time, to generate full thermodynamic phase diagrams for ITZ/polymer systems, taking into account isotropic and anisotropic phases that this drug can form. It was found that supercooled ITZ does not form an amorphous but a vitrified smectic (vSm) phase with a glass transition temperature of 59.35 °C (determined using a 10 °C/min heating rate), as is evident from X-ray diffraction and thermomicroscopic (PLM) experiments. Two endothermic LC events with the onset temperature values for a smectic to nematic transition of 73.2 ± 0.4 °C and a nematic to isotropic transformation at 90.4 ± 0.35 °C and enthalpies of transition of 416 ± 34 J/mol and 842 ± 10 J/mol, respectively, were recorded. For the binary supercooled mixtures, PLM and differential scanning calorimetry showed a phase separation with birefringent vSm persistent over a wide polymer range, as noticed especially for the hypromellose acetate succinate (HAS) systems. Both, smectic and nematic, phases were detected for the supercooled ITZ/HAS and ITZ/methacrylic acid–ethyl acrylate copolymer (EUD) mixtures, while geometric restrictions inhibited the smectic formation in the ITZ/poly(acrylic acid) (CAR) systems. The Flory–Huggins lattice theory coupled with the Maier–Saupe–McMillan approach to model anisotropic ordering of molecules was successfully utilized to create phase diagrams for all ITZ/polymer mixtures. It was concluded that in a supercooled ITR/polymer mix, if ITZ is present in a LC phase, immiscibility as a result of molecule anisotropy is afforded. This study shows that the LC nature of ITZ cannot be disregarded when designing stable formulations containing this molecule." @default.
• W2893056265 created "2018-10-05" @default.
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• W2893056265 date "2018-09-25" @default.
• W2893056265 modified "2023-09-26" @default.
• W2893056265 title "Phase Diagrams of Polymer-Dispersed Liquid Crystal Systems of Itraconazole/Component Immiscibility Induced by Molecular Anisotropy" @default.
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• W2893056265 doi "https://doi.org/10.1021/acs.molpharmaceut.8b00724" @default.
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