Purification of an ascomycin derivative with simulated moving bed chromatography. A case study.
A purification process was developed for the separation of a semi-synthetic ascomycin derivative from its by-products. The process consists of a silica gel filtration and crystallization step prior to two simulated moving bed (SMB) separations, where in the first part the polar by-products and in the second part the apolar by-products were removed. The desired purity was achieved in a final crystallization step. Key elements of the whole process were the design of the first crystallization to obtain a product feasible for SMB chromatography and the specification of operating parameters for the two corresponding SMB steps. Starting from a crude product with an assay of only 44.9% an overall yield for the whole process of 81.0% was achieved with a final purity of >98%.
Küsters
E
E
Chemical and Analytical Development, Novartis Pharma AG, Basel, Switzerland. ernst.kuesters@pharma.novartis.com
Heuer
C
C
Wieckhusen
D
D
D002850:Chromatography, Gel / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003460:Crystallization; D058428:Silica Gel; D012822:Silicon Dioxide / Q000737:chemistry; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification
D058428:Silica Gel; D012822:Silicon Dioxide; C058028:immunomycin; D016559:Tacrolimus