Metastable Racemic Ibuprofen Supercooled Liquid

Amorphous solid dispersions are good candidates for improving solubility in water and the oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). Amorphous solids become supercooled liquids when the temperature reaches the glass transition temperature (T<sub>g<...

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Main Authors: Tuanjia Li, Wangchuan Xiao, Shizhao Ren, Rongrong Xue, Fenghua Chen
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Crystals
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Online Access:https://www.mdpi.com/2073-4352/14/12/1037
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author Tuanjia Li
Wangchuan Xiao
Shizhao Ren
Rongrong Xue
Fenghua Chen
author_facet Tuanjia Li
Wangchuan Xiao
Shizhao Ren
Rongrong Xue
Fenghua Chen
author_sort Tuanjia Li
collection DOAJ
description Amorphous solid dispersions are good candidates for improving solubility in water and the oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). Amorphous solids become supercooled liquids when the temperature reaches the glass transition temperature (T<sub>g</sub>). For APIs with low melting points, T<sub>g</sub> can be below room temperature, which makes it difficult to prepare long-term stable amorphous solids. Studies on the physicochemical properties of supercooled liquids shed light on the design of ASDs for APIs with low melting points. Racemic ibuprofen (IBU) supercooled liquid has been detected using differential scanning calorimetry and powder X-ray diffraction during the melt-quenching of IBU at a low temperature (0 °C). In this work, gram-scaled IBU supercooled liquid was prepared using the melt-quenching method, maintaining a liquid state for minutes at room temperature and for hours at 10 °C, as confirmed by visual observation. The Raman spectra, IR spectra, and UV-vis spectra results indicate that the structure of the IBU supercooled liquid is similar to that of an IBU solution instead of IBU Form I. The rate of recrystallization into Form I can be adjusted by controlling the temperature and additives, as confirmed by visual observation. Moreover, long-term stable IBU dispersions, with improved aqueous solubility, were inspired by the IBU supercooled liquid. The IBU supercooled liquid model can guide the preparation of ASDs for low melting point drugs.
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institution Kabale University
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language English
publishDate 2024-11-01
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series Crystals
spelling doaj-art-b3c96fd713ea42bd9c6742a7458cb2da2024-12-27T14:19:41ZengMDPI AGCrystals2073-43522024-11-011412103710.3390/cryst14121037Metastable Racemic Ibuprofen Supercooled LiquidTuanjia Li0Wangchuan Xiao1Shizhao Ren2Rongrong Xue3Fenghua Chen4College of Material Engineering, Fujian Agriculture and Forestry University, Fuzhou 350100, ChinaSchool of Resources and Chemical Engineering, Sanming University, Sanming 365004, ChinaSchool of Resources and Chemical Engineering, Sanming University, Sanming 365004, ChinaSchool of Resources and Chemical Engineering, Sanming University, Sanming 365004, ChinaSchool of Resources and Chemical Engineering, Sanming University, Sanming 365004, ChinaAmorphous solid dispersions are good candidates for improving solubility in water and the oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). Amorphous solids become supercooled liquids when the temperature reaches the glass transition temperature (T<sub>g</sub>). For APIs with low melting points, T<sub>g</sub> can be below room temperature, which makes it difficult to prepare long-term stable amorphous solids. Studies on the physicochemical properties of supercooled liquids shed light on the design of ASDs for APIs with low melting points. Racemic ibuprofen (IBU) supercooled liquid has been detected using differential scanning calorimetry and powder X-ray diffraction during the melt-quenching of IBU at a low temperature (0 °C). In this work, gram-scaled IBU supercooled liquid was prepared using the melt-quenching method, maintaining a liquid state for minutes at room temperature and for hours at 10 °C, as confirmed by visual observation. The Raman spectra, IR spectra, and UV-vis spectra results indicate that the structure of the IBU supercooled liquid is similar to that of an IBU solution instead of IBU Form I. The rate of recrystallization into Form I can be adjusted by controlling the temperature and additives, as confirmed by visual observation. Moreover, long-term stable IBU dispersions, with improved aqueous solubility, were inspired by the IBU supercooled liquid. The IBU supercooled liquid model can guide the preparation of ASDs for low melting point drugs.https://www.mdpi.com/2073-4352/14/12/1037ibuprofensupercooled liquidstabilitydissolutionamorphous solid dispersions
spellingShingle Tuanjia Li
Wangchuan Xiao
Shizhao Ren
Rongrong Xue
Fenghua Chen
Metastable Racemic Ibuprofen Supercooled Liquid
Crystals
ibuprofen
supercooled liquid
stability
dissolution
amorphous solid dispersions
title Metastable Racemic Ibuprofen Supercooled Liquid
title_full Metastable Racemic Ibuprofen Supercooled Liquid
title_fullStr Metastable Racemic Ibuprofen Supercooled Liquid
title_full_unstemmed Metastable Racemic Ibuprofen Supercooled Liquid
title_short Metastable Racemic Ibuprofen Supercooled Liquid
title_sort metastable racemic ibuprofen supercooled liquid
topic ibuprofen
supercooled liquid
stability
dissolution
amorphous solid dispersions
url https://www.mdpi.com/2073-4352/14/12/1037
work_keys_str_mv AT tuanjiali metastableracemicibuprofensupercooledliquid
AT wangchuanxiao metastableracemicibuprofensupercooledliquid
AT shizhaoren metastableracemicibuprofensupercooledliquid
AT rongrongxue metastableracemicibuprofensupercooledliquid
AT fenghuachen metastableracemicibuprofensupercooledliquid