Process Parameters in the Purification of Curcumin by Cooling Crystallization

Purification of crude curcumin by up to four successive cooling crystallizations has been investigated for a wide variety of process conditions. For each crystallization step the influence of various processing conditions on crystal purity, polymorphic outcome, and crystal size and shape is reported. By an extensive number of experiments according to a statistical experimental design, the influence on cooling rate, seeding, seed polymorph, and agitation conditions has been identified. Slow cooling and seeding, particularly with the metastable Form II seed, significantly improves the purification. A correlation between product crystal size and purity is found. By tuning the crystallization parameters the number of recrystallization steps required to reach a certain purity can be reduced, which significantly increased the overall curcumin yield from 28% to 50%.