GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy , National University of Singapore , 18 Science Drive 4 , Singapore 117543.
Mol Pharm. 2018 Apr 2;15(4):1635-1642. doi: 10.1021/acs.molpharmaceut.8b00007. Epub 2018 Mar 6.
Surface roughness is well recognized as a critical physical property of particulate systems, particularly in relation to adhesion, friction, and flow. An example is the surface property of carrier particles in carrier-based dry powder inhaler (DPI) formulations. The numerical characterization of roughness remains rather unsatisfactory due to the lack of spatial (or length scale) information about surface features when a common amplitude parameter such as average roughness ( R) is used. An analysis of the roughness of lactose carrier particles at three different length scales, designed for specificity to the study of interactive mixtures in DPI, was explored in this study. Three R parameters were used to represent the microscale, intermediate scale, and macroscale roughness of six types of surface-modified carriers. Coating of micronized lactose fines on coarse carrier particles increased their microroughness from 389 to 639 nm while the macroroughness was not affected. Roller compaction at higher roll forces led to very effective surface roughening, particularly at longer length scales. Changes in R parameters corroborated the visual observations of particles under the scanning electron microscope. Roughness at the intermediate scale showed the best correlation with the fine particle fraction (FPF) of DPI formulations. From the range of 250 to 650 nm, every 100 nm increase in the intermediate roughness led to ∼8% increase in the FPF. However, the effect of surface roughness was greatly diminished when fine lactose (median size, 9 μm) of comparable amounts to the micronized drug were added to the formulation. The combination of roughness parameters at various length scales provided much discriminatory surface information, which then revealed the "quality" of roughness necessary for improving DPI performance.
表面粗糙度是颗粒系统的一个重要物理特性，尤其是在与粘附、摩擦和流动有关的情况下。例如，载体颗粒在载体干粉吸入器 (DPI) 制剂中的表面特性。由于在使用常用的幅度参数（如平均粗糙度 (R)）时缺乏有关表面特征的空间（或长度尺度）信息，因此对粗糙度的数值表征仍然相当不理想。本研究探讨了在三个不同长度尺度上对乳糖载体颗粒的粗糙度进行分析，这些长度尺度是为了专门研究 DPI 中的相互作用混合物而设计的。使用三个 R 参数来表示六种表面改性载体的微尺度、中尺度和大尺度粗糙度。将超细乳糖细粉涂覆在粗载体颗粒上，会使它们的微粗糙度从 389nm 增加到 639nm，而大粗糙度则不受影响。在较高的轧辊力下进行滚压会导致非常有效的表面粗糙化，特别是在较长的长度尺度上。R 参数的变化与扫描电子显微镜下观察到的颗粒变化一致。中尺度粗糙度与 DPI 制剂的细颗粒分数 (FPF) 相关性最好。从中尺度的 250nm 到 650nm 范围内，每增加 100nm 的中间粗糙度，FPF 会增加约 8%。然而，当制剂中添加与微米级药物相当数量的细乳糖（中值粒径为 9μm）时，表面粗糙度的影响大大降低。在各种长度尺度上的粗糙度参数的组合提供了更多有区别的表面信息，从而揭示了改善 DPI 性能所需的“质量”粗糙度。
