Development and Scale-up of a Seeded Acidic Co-Addition Crystallization

An isolation of a previously unisolated nucleoside HCl salt intermediate was developed using PAT in which the intermediate compound was recrystallized via an aqueous acidic and DMSO saturated solution seeded co-addition crystallization. Typical isolation via exclusively anti-solvent driven crystallization resulted in needle like morphology translating to poor isolation characteristics. Crystallization by seeded co-addition resulted in particles with markedly improved morphology and isolation characteristics. The process was successfully scaled-up in an accelerated manner from lab (0.5L) to pilot plant (200L) to production (8000L) in 4 months.