Resolution of Omeprazole Using Coupled Preferential Crystallization: Efficient Separation of a Nonracemizable Conglomerate Salt under Near-Equilibrium Conditions

Abstract

A facile and efficient resolution of omeprazole as the monopotassium salt diethanol solvate using coupled preferential crystallization has been developed. This approach uses small perturbations in solution-phase concentration to control the competing process of selective crystal growth while suppressing unwanted primary nucleation. The result is a selective crystallization technique that replaces the traditional batch-type isolation with a continuous process amenable to scale, which provides easy access to enantiopure conglomerate crystals.

Enantioseparation, Stereochemical Assignment and Chiral Recognition Mechanism of Sulfoxide-Containing Drugs

“…In the last two decades, hundreds of papers reported the chiral separation methods of sulfoxides including capillary electrophoresis [ 11 , 12 ], chemical resolution [ 13 , 14 ], HPLC [ 15 , 16 , 17 , 18 ], and supercritical fluid chromatography [ 19 , 20 ]. Amongst all, we focused on chiral HPLC, which might be a favorable and effective way for both analytical and preparative separations of chiral compounds [ 21 ].…”

Stereoselective Crystallization as a Basis for Single‐Enantiomer Drug Production

“…The registered racemic forms of omeprazole 29 , free acid and its magnesium salt, are not prone to spontaneous resolution. At the same time, the omeprazole potassium salt solvates with two molecules of ethanol can be separated into individual enantiomers by direct methods: in batch crystallization mode and in continuous mode .…”

Advances in Organic Crystal Chemistry

“…The crystals of the pure enantiomers used as seed are somewhat larger and thus less soluble. 21.15 [88]. 21.14).…”