Farzan Maryam, Roth Roger, Québatte Gabriela, Schoelkopf Joachim, Huwyler Jörg, Puchkov Maxim
Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
Fundamental research, Omya International AG, 4665 Oftringen, Switzerland.
Pharmaceutics. 2019 Jan 15;11(1):32. doi: 10.3390/pharmaceutics11010032.
Accurate analysis of intraparticle distribution of substances within porous drug carriers is important to optimize loading and subsequent processing. Mercury intrusion porosimetry, a common technique used for characterization of porous materials, assumes cylindrical pore geometry, which may lead to misinterpretation. Therefore, imaging techniques such as focused ion beam scanning electron microscopy (FIB-SEM) help to better interpret these results. The purpose of this study was to investigate the differences between mercury intrusion and scanning electron microscopy and to identify the limitations of each method. Porous microparticles, functionalized calcium carbonate, were loaded with bovine serum albumin and dipalmitoylphosphatidylcholine (DPPC) by solvent evaporation and results of the pore size distribution obtained by both methods were compared. The internal structure of the novel pharmaceutical excipient, functionalized calcium carbonate, was revealed for the first time. Our results demonstrated that image analysis provides a closer representation of the material distribution since it was possible to discriminate between blocked and filled pores. The physical nature of the loaded substances is critical for the deposition within the pores of functionalized calcium carbonate. We conclude, that a combination of mercury intrusion porosimetry and focused ion beam scanning electron microscopy allows for a reliable analysis of sub-micron porous structures of particulate drug carriers.
准确分析多孔药物载体内部物质的颗粒内分布对于优化负载及后续加工十分重要。压汞法是一种常用于表征多孔材料的技术，它假定孔隙几何形状为圆柱形，这可能会导致误解。因此，诸如聚焦离子束扫描电子显微镜（FIB-SEM）等成像技术有助于更好地解释这些结果。本研究的目的是探究压汞法与扫描电子显微镜之间的差异，并确定每种方法的局限性。通过溶剂蒸发法将多孔微粒（功能化碳酸钙）负载牛血清白蛋白和二棕榈酰磷脂酰胆碱（DPPC），并比较两种方法获得的孔径分布结果。首次揭示了新型药用辅料功能化碳酸钙的内部结构。我们的结果表明，图像分析能够更准确地反映材料分布，因为可以区分堵塞的孔隙和填充的孔隙。负载物质的物理性质对于在功能化碳酸钙孔隙内的沉积至关重要。我们得出结论，压汞法和聚焦离子束扫描电子显微镜相结合能够可靠地分析颗粒药物载体的亚微米多孔结构。
