Loading of Porous Functionalized Calcium Carbonate Microparticles: Distribution Analysis with Focused Ion Beam Electron Microscopy and Mercury Porosimetry

Abstract

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.