Method of purifying tacrolimus
OwnerVilmos Keri, Andrea Csorvasi +2inventors
InventorsVilmos Keri, Andrea Csorvasi, Istvan Melczer, Angela Simon
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Abstract
The invention provides pure tacrolimus and a method for purifying tacrolimus in which a loading charge of tacrolimus is placed in juxtaposition with a bed of wet sorption resin, the loading charge and bed are eluted with an eluent comprising THF, acetonitrile, or a combination thereof, water, and, optionally, at least one additional organic solvent, the heart cut of the eluent is collected, and tacrolimus is collected, the tacrolimus is further crystallized and recrystallized until obtaining a reduced level of impurities.
Claims36
Tacrolimus having a total impurities content of less than about 0.50 area percent by HPLC.
Tacrolimus having less than about 0.06 area percent by HPLC of ascomycin.
Tacrolimus having less than about 0.07 area percent by HPLC of dihydrotacrolimus.
Tacrolimus having less than about 0.02 area percent by HPLC of the impurity RRT 1.19.
Tacrolimus having less than about 0.12 area percent by HPLC of the impurity RRT 0.60.
Tacrolimus having less than about 0.12 area percent by HPLC of the impurity RRT 0.83.
Tacrolimus having less than about 0.08 area percent by HPLC of the impurity RRT 1.45.
Tacrolimus having less than about 0.06 area percent by HPLC of any individual impurity.
A process for purifying tacrolimus comprising:
- a) providing a loading charge of tacrolimus;
- b) loading the loading charge of the tacrolimus onto a bed of sorption resin;
- c) eluting the loading charge and bed with an eluent comprising THF, acetonitrile, or a combination thereof, and water to obtain an effluent;
- d) collecting the main fraction of the effluent;
- e) recovering the tacrolimus from the main fraction;
- f) crystallizing the tacrolimus;
- and
- g) recrystallizing the tacrolimus.
Dependencies are inferred from the claim text.