Preparation of orlistat and orlistat crystalline forms
AssigneeBiogal Gyogyszergyar Rt.
InventorsVilmos Keri, Andrea Csorvasi, Judith Aronhime
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Abstract
The present invention is directed to a process of converting lipstatin to orlistat by catalytic hydrogenation. The present invention further discloses novel crystalline solid orlistat forms, designated form I and form II and methods for their preparation.
Claims47
A process of preparing orlistat, comprising the steps of hydrogenating lipstatin in an organic solvent in the presence of a catalyst to obtain orlistat.
A crystalline solid orlistat, or hydrate or solvate thereof, characterized by data selected from the group consisting of a XRD pattern with peaks at 5.8, 18.5, 19.5 and 22.3±0.2 degrees two-theta and a DSC melting endotherm at about 46.7° C.
A crystalline solid orlistat, or hydrate or solvate thereof, characterized by data selected from the group consisting of a XRD pattern with peaks at 4.8, 5.6, 14.9, 17.3, 19.2 and 22.0±0.2 degrees two-theta, and a DSC melting endotherm at about 46.6° C.
A process of preparing crystalline solid orlistat, or hydrate or solvate thereof, characterized by data selected from the group consisting of a XRD pattern with peaks at 5.8, 18.5, 19.5 and 22.3±0.2 degrees two-theta and a DSC melting endotherm at about 46.7° C., comprising the steps of:
- (a) dissolving orlistat in a solvent;
- (b) adding an anti-solvent or water to the solvent;
- and
- (c) isolating the crystalline solid orlistat.
A process for preparing a crystalline solid orlistat, or hydrate or solvate thereof, characterized by data selected from the group consisting of a XRD pattern with peaks at 4.8, 5.6, 14.9, 17.3, 19.2 and 22.0±0.2 degrees two-theta, and a DSC melting endotherm at about 46.6° C., comprising the steps of:
- (a) mixing orlistat in hexane to form a mixture at a first temperature;
- (b) lowering the first temperature of the mixture sufficiently to precipitate;
- and
- (c) isolating crystalline solid orlistat.
A process of preparing a mixture of crystalline solid orlistat, or hydrate or solvate thereof, characterized by data selected from the group consisting of a XRD pattern with peaks at 5.8, 18.5, 19.5 and 22.3±0.2 degrees two-theta, a DSC melting endotherm at about 46.7° C., a XRD pattern with peaks at 4.8, 5.6, 14.9, 17.3, 19.2 and 22.0±0.2 degrees two-theta, and a DSC melting endotherm at about 46.6° C., comprising the steps of:
- (a) dissolving orlistat in a solvent;
- and
- (b) inducing crystallization to obtain the mixture of crystalline solid orlistat.
A process of preparing orlistat, comprising the steps of:
- a) preparing fermentation broth containing lipstatin;
- b) extracting lipstatin from the fermentation broth;
- c) hydrogenating the lipstatin to obtain orlistat;
- and
- d) separating the orlistat.
Dependencies are inferred from the claim text.