Faculty of Pharmaceutical Science, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Int J Pharm. 2012 Jan 17;422(1-2):245-53. doi: 10.1016/j.ijpharm.2011.11.005. Epub 2011 Nov 10.
The aim of this work was to characterize the solid-state properties of fusidic acid (FA).
Solid forms of FA were prepared by solvent-mediated polymorphic transformation of commercial FA (Form III) in acetonitrile (ACN), and methanol:H(2)O (50:50), or generated by solvent recrystallization from dichloromethane (DCM). Polymorphs were characterized using, X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), polarizing hot stage microscopy (HSM), and intrinsic dissolution rate (IDR).
Slurrying commercial FA (Form III) in methanol:H(2)O (50:50), yielded a metastable form (Form IV). This metastable form converts to Form I or back to Form III in ACN and H(2)O, respectively, and Form II upon recrystallization from DCM. IDR of Form IV was 0.092 mg/min/cm(2), and was statistically different (p<0.05) from the IDR of Forms I, II, and III, with IDR of 0.053, 0.043, and 0.045mg/min/cm(2), respectively. The amorphous FA had an IDR of 0.125 mg/min/cm(2), and was significantly higher (p<0.05) than any other solid form. There were no statistical differences in the IDR of Form I, II, or III.
This work provides evidence for the existence of two previously unreported polymorphic forms of FA (Forms II and IV) and an amorphate.
本工作旨在研究游离酸（FA）的固态特性。
通过在乙腈（ACN）和甲醇：水（50:50）中溶剂介导的多晶型转化，以及从二氯甲烷（DCM）溶剂重结晶制备 FA 的固体形式。使用 X 射线衍射（XRD）、差示扫描量热法（DSC）、热重分析（TGA）、偏光热台显微镜（HSM）和固有溶解速率（IDR）对多晶型物进行了表征。
将商业 FA（Form III）在甲醇：水（50:50）中搅拌，得到一种亚稳形式（Form IV）。这种亚稳形式在 ACN 和 H2O 中分别转化为 Form I 或返回到 Form III，而在 DCM 中重结晶则转化为 Form II。Form IV 的 IDR 为 0.092mg/min/cm2，与 Form I、II 和 III 的 IDR （分别为 0.053、0.043 和 0.045mg/min/cm2）相比具有统计学差异（p<0.05）。无定形 FA 的 IDR 为 0.125mg/min/cm2，明显高于任何其他固体形式（p<0.05）。Form I、II 或 III 的 IDR 之间无统计学差异。
本工作为游离酸（FA）存在两种以前未报道的多晶型形式（Form II 和 IV）和无定形物提供了证据。
