Precise particle size control during spherical agglomeration of benzoic acid by modification of the bridging liquid phase using TWEEN 20

Abstract

The interest in spherical agglomeration processes in the pharmaceutical industry is rising due to the possibility of direct tableting of Active Pharmaceutical Ingredients and enhancements in bulk powder properties translating into improved powder processability. While agglomerating needle-shaped particles into spheres offers numerous advantages, such as improved flowability, filterability, and particle density, achieving precise control over the particle size and shape of the agglomerates remains a significant challenge. More specifically, the obtained agglomerate size rarely reaches values below 500 μm, which is the desired size range for pharmaceutical applications. To address this challenge, the current research investigates the effectiveness of incorporating surfactants at varying concentrations as a means to control the particle size and shape of the resulting agglomerates. Reversed addition antisolvent crystallization experiments were performed in ethanol/water using benzoic acid as a model compound, followed by the addition of a bridging liquid (toluene), which wets and bridges the single crystals into agglomerates. To modify the interfacial tension between the two immiscible liquid phases, different concentrations of the tween 20 surfactant were used, leading to a range of interfacial tensions spanning from 0.50 to 16.38 × 10−3 N/m. Both crystallization and agglomeration processes were monitored in situ using in-process microscopy tools. The experimental results demonstrated that by adjusting the surfactant concentration and thus the corresponding interfacial tension of the bridging liquid, highly tunable agglomerate sizes were achieved, ranging from 160 μm to 4412 μm. A higher surfactant concentration is correlated with smaller agglomerates and is key to control the final agglomerate size. However, it should be noted that the introduction of surfactants in the spherical agglomeration process negatively impacted the agglomerate's strength. Nonetheless, this method remains a promising and innovative technique for controlling the final particle size during spherical agglomeration.