Spherical agglomeration of benzoic acid using membrane emulsification

Spherical agglomeration (SA) is a key crystal shape modification technique commonly used to improve processability and physical properties of active pharmaceutical ingredients (APIs), such as flowability and dissolution. SA involves the introduction of a bridging liquid in the form of droplets into a suspension of API crystals. A novel approach was successfully implemented in this study by adopting a membrane emulsification (ME) system to control the size of bridging liquid droplets and spherical agglomerates. The study investigated ways to achieve the critical quality attributes of the spherical agglomerates by varying operating conditions and design parameters, including mixing rate, bridging liquid injection rate and membrane pore diameter. Antisolvent crystallization of benzoic acid in ethanol (solvent) and water (antisolvent) in presence of toluene as a bridging liquid was used as a case study. Spherical agglomerates of benzoic acid with enhanced quality attributes and mean size of 300 µm were obtained using a membrane pore size of 18 µm, a bridging liquid flow rate of 0.025 mL/min and mixing rate in the range of 800 RPM and 1000 RPM.