CRYSTAL GROWTH & DESIGN
·
2024
·
IF 3.2
Kangning Sun,Peizhuo Han,Changlin Yao,Yaning Zhao,Chuanchi Zhang,Yao Zhang,Jingke Jiang,Lei Wang
Molecules at the liquid/vapor interface have different properties, such as faster mobility and special packing structure, which can potentially affect crystal nucleation. However, the surface effect varies significantly among different small organic molecules and the underlying mechanism is still poorly understood. Herein, the effect of the surface on the crystal nucleation dynamics has been investigated in the glass-forming liquid molnupiravir (MPV) by measuring the crystal nucleation rates at the surface and in the bulk. It was found that the surface of the glass-forming liquid MPV could significantly enhance the nucleation rate by around six orders of magnitude without a polymorphic change. In comparison to water and acetaminophen with a surface enhancement factor of Js/Jv ≈ 105, the larger surface enhancement factor of MPV indicates a higher similarity between the nucleated crystal structure and the molecular packing at the surface. Our work enriches the surface-enhanced nucleation systems, which are beneficial to further understanding the stability of amorphous drugs.
研究领域:
材料科学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2024
·
IF 3.2
Peizhuo Han,Lei Wang,Shuhong Song,Changlin Yao,Xutang Tao,Guanying Xie,Huimin Li,Yaqian Qu,Hongshuai Wang,Zeliang Gao,Yanyan Sun,Huachang Wu,Weiguo Song
Molnupiravir (MPV) is a widely used oral anti-COVID-19 drug. Owing to the rotatable bonds and the large number of acceptors and donors of hydrogen bonds in the molecular structure of MPV, three pure polymorphs (forms I, II, and III) and four solvates (ethanol, isopropanol, isobutanol, and tetrahydrofuran) of MPV (MPV-EtOH, MPV-IPA, MPV-IBA, and MPV-THF) were obtained. Importantly, the crystal structures of form I and the four solvates were successfully determined by single-crystal X-ray diffraction for the first time. Interestingly, all solvates are isostructural and have very similar unit cell parameters. Meanwhile, the solvent molecules in their structures are all in the voids surrounded by MPV molecules, forming a channel structure that facilitates desolvation. The formation mechanism of the solvates was also investigated based on the molecular electrostatic potential and hydrogen-bond energy of possible synthons. Moreover, a detailed stability study of MPV was conducted by using thermal analysis and dynamic vapor sorption. Finally, the phase transformations of the different solid forms were summarized. Our study provides a comprehensive understanding of the crystal landscape of the MPV.
研究领域:
药物化学
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晶体学
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生物医学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Peizhuo Han,Lei Wang,Huimin Li,Changlin Yao,Yaqian Qu,Xu Zhang,Hanlin Zhao,Yaqi Ren,Bozhang Li,Lufeng Xu,Weiguo Song,Xutang Tao
Molnupiravir (MPV) is an oral antiviral drug widely used for the treatment of coronavirus disease 2019 (COVID-19). However, the commercial form I of MPV has a poor tabletability, greatly restricting its manufacture. To solve this problem, a new cocrystal named MPV-caprolactam (CPL) was discovered by melt crystallization, and its crystal structure was successfully determined by single crystal X-ray diffraction. Meanwhile, the formation mechanism of the MPV-CPL cocrystal was studied via the formation enthalpies, and the negative formation enthalpy (−27.61 J/g at 25 ℃) is responsible for the crystallization of the MPV-CPL cocrystal. Finally, the powder tableting properties of the MPV-CPL cocrystal were investigated, and the MPV-CPL cocrystal has superior tabletability, achieving a tensile strength of 2.06 ± 0.09 MPa at 262.5 MPa compression pressure — a 1.93-fold increase over pure MPV. The MPV-CPL cocrystal also shows good compressibility, compactibility, and plasticity. This work establishes two key advances: (1) melt crystallization is a supplement to solution methods, and it can produce pharmaceutical cocrystals that tend to form solvates in solution, and (2) the improvement in tabletability of MPV-CPL cocrystal overcomes the main barrier in developing MPV tablets, which makes it a promising candidate for developing MPV tablets.
研究领域:
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）