International Journal of Pharmaceutics ( IF 5.8 ) Pub Date : 2021-09-01 , DOI: 10.1016/j.ijpharm.2021.121067 Iryna Andrusenko 1 , Victoria Hamilton 2 , Arianna E Lanza 1 , Charlie L Hall 2 , Enrico Mugnaioli 1 , Jason Potticary 2 , Asma Buanz 3 , Simon Gaisford 3 , Anna M Piras 4 , Ylenia Zambito 4 , Simon R Hall 2 , Mauro Gemmi 1
The structure solution of the δ-polymorph of indomethacin was obtained using three-dimensional electron diffraction. This form shows a significantly enhanced dissolution rate compared with the more common and better studied α- and γ-polymorphs, indicating better biopharmaceutical properties for medicinal applications. The structure was solved in non-centrosymmetric space group P21 and comprises two molecules in the asymmetric unit. Packing and molecule conformation closely resemble indomethacin methyl ester and indomethacin methanol solvate. Knowledge of the structure allowed the rational interpretation of spectroscopic IR and Raman data for δ-polymorph and a tentative interpretation for still unsolved indomethacin polymorphs. Finally, we observed a solid–solid transition from δ-polymorph to α-polymorph that can be driven by similarities in molecular conformation.
中文翻译:
δ-吲哚美辛的结构测定、热稳定性和溶出度
使用三维电子衍射获得了吲哚美辛δ-多晶型物的结构解。与更常见和更好研究的α-和γ-多晶型物相比,这种形式显示出显着提高的溶出率,表明药物应用的生物制药特性更好。在非中心对称空间群P 2 1 中解出结构并且在不对称单元中包含两个分子。填料和分子构象与吲哚美辛甲酯和吲哚美辛甲醇溶剂化物非常相似。对结构的了解允许对 δ-多晶型物的光谱红外和拉曼数据进行合理解释,并对仍未解决的吲哚美辛多晶型物进行初步解释。最后,我们观察到从 δ-多晶型物到 α-多晶型物的固-固转变,这可以由分子构象的相似性驱动。