Habit modification of tamoxifen crystals using antisolvent crystallizations

摘要

The crystal habit of tamoxifen was modified using antisolvent crystallization techniques. Tamoxifen was crystallized from organic solvents using two different antisolvents (water and carbon dioxide). The habit of the precipitated crystals was modified by changing the process conditions, such as the solution and antisolvent mixing rate, the organic solvent, the presence of ultrasonic waves, and the addition of external additives. Particle size, crystal habit, particle aspect ratio and powder XRD patterns of the precipitated tamoxifen crystals were measured. With water as the antisolvent, the particle size of tamoxifen was significantly reduced compared to that of the raw material. When the antisolvent was carbon dioxide, the particle size was an order of magnitude greater than that of the raw material. The average aspect ratio of the tamoxifen crystals ranged from 1.8 to 16.2. The presence of ultrasonic waves caused a significant reduction in the aspect ratio, as well as the particle size. Furthermore, the addition of external additives was found to influence the crystal habit of tamoxifen.