Optimizing the Aspect Ratio of Cephalexin in Reactive Crystallization by Controlling Supersaturation and Seeding Policy

Batch crystallization in acidic aqueous solution of cephalexin was conducted by reactive crystallization with or without seeding. Supersaturation was generated by mixing ammonia and acidic aqueous solution of cephalexin and controlled by solution feeding rate and seeding conditions. UV and Morphologi G3 were used to measure supersaturation and aspect ratio. Experimental results demonstrated that burst nucleation occurred and the products were needle-like at high supersaturation; meanwhile, the products were plate-like and had high aspect ratio at low supersaturation. Analysis of the measured supersaturation profiles and corresponding aspect ratio explained the mechanisms governing the aspect ratio. The optimized operating parameters were also proposed (seeding supersaturation is equal to 1.3, seed mass ratio 8% and feeding rate 368 μL/min).