Production of functional spherical particles with porous hollow structures in water via oiling-out directional agglomeration†

Porous hollow spherical particles benefit from special structural features and fascinating physicochemical properties resulting in widespread application. Particularly in pharmaceutical engineering, they have significant advantages for direct compression and drug combination. However, their large-scale application is severely hindered by the limitations of traditional production methods in terms of the use of complex equipment, high energy consumption and high organic solvent usage. In this work, we have developed an oiling-out directional agglomeration method to produce porous hollow indomethacin spherical particles by a simple heating–quenching–drying operation without the use of organic solvents and templating agents. Compared to commercial flake crystals, the indomethacin spherical products have higher average tensile strength (471% increase) and higher plastic deformability, i.e. better tabletability and compressibility. More importantly, nifedipine is successfully loaded into porous hollow indomethacin spherical particles based on molecular polarity differences. The composite particles with a core–shell structure exhibit excellent powder properties, tableting and anti-degradation performance, while also achieving sequential release of drugs. This contribution provides the basis for the development of drug formulation strategies and the design of functional crystalline materials.