Microstructures and pharmaceutical properties of ferulic acid agglomerates prepared by different spherical crystallization methods

Spherical agglomerates of an active pharmaceutical ingredient, ferulic acid (FA), were prepared using four different spherical crystallization methods, i.e., quasi-emulsion solvent diffusion (QESD), anti-solvent, pH shift, and the direct method. Both the as-received FA and spherical agglomerates were characterized in terms of specific surface area (SSA), primary crystal shape and size, granule morphology and size, powder flowability, tabletability at two distinct speeds, and dissolution (both powder and tablet). Results showed that the microstructure, which is affected by size, shape, and packing of primary crystals, was the key that determined the flowability, tabletability and dissolution. The QESD powder exhibited the best flowability and tabletability. Both powder and tablet dissolution of FA followed the order of as-received > QESD > anti-solvent > pH shift, which was consistent with the order of the surface area exposed to the dissolution medium and not SSA. Moreover, compression reduced differences in the rates of dissolution of FA powders due to the size reduction of agglomerates by fragmentation.