Analytical Development, Pharmaceutical Sciences, Takeda Pharmaceutical Company Limited, 2-26-1, Muraoka-Higashi, Fujisawa, Kanagawa 251-8555, Japan.
Department of Molecular Pharmaceutics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
Int J Pharm. 2022 Jun 10;621:121784. doi: 10.1016/j.ijpharm.2022.121784. Epub 2022 Apr 30.
The states of amorphous drug and/or newly generated crystalline drug on the surface of amorphous drug samples must be carefully characterized to validate the quality of pharmaceutical amorphous drugs. In this study, we investigated whether individual mechanical properties of amorphous and crystalline drugs could be discerned by an atomic force microscope (AFM) with a mapping. Among mechanical properties, the amorphous and crystal drugs were quantitatively distinguished by elastic modulus using PeakForce quantitative nanomechanical mapping. The elastic modulus of the crystals exceeded 10 GPa-significantly higher than that of the amorphous, which was ≤5 GPa in all five model drugs; consequently, ≤200 nm scale crystals were detected on amorphous surfaces. Furthermore, the elastic modulus reflected the difference in the amorphous states between the molten and the solvent-evaporated preparations in the microscopic area, thereby demonstrating the ability of AFM to characterize amorphous states. Taken together, AFM measurements using elastic modulus can be an effective analytical tool to provide microscale mapping and characterization of amorphous surfaces, leading to enhanced amorphous drug development.
必须仔细表征无定形药物样品表面上的无定形药物和/或新生成的晶态药物的状态，以验证药物无定形的质量。在这项研究中，我们研究了原子力显微镜（AFM）是否可以通过映射来辨别无定形和晶态药物的单个机械性能。在机械性能中，使用 PeakForce 定量纳米力学映射法通过弹性模量对无定形和晶体药物进行定量区分。晶体的弹性模量超过 10 GPa-明显高于所有五种模型药物中的无定形，其弹性模量均≤5 GPa；因此，在无定形表面上检测到≤200nm 尺度的晶体。此外，弹性模量反映了微观区域中熔融和溶剂蒸发制剂之间无定形状态的差异，从而证明了 AFM 表征无定形状态的能力。总之，使用弹性模量的 AFM 测量可以成为一种有效的分析工具，用于提供无定形表面的微尺度映射和表征，从而促进无定形药物的开发。
