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US 2016/0355525 A1Published application
Process for preparation of darunavir
AssigneeLaurus Labs Private Limited
InventorsKAMESWAR R. CHIVUKULA, Venkata R. MURTHY, Venkata S. INDUKURI, Seeta R. GORANTLA
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Abstract
The present invention provides a process for the preparation of darunavir or solvates or a pharmaceutically acceptable salt thereof substantially free of bisfuranyl impurities, particularly darunavir propionate solvate. The present invention also provides a process for preparation amorphous darunavir using the darunavir propionate solvate.
Claims20
1-12:
- (canceled)
13:
- Darunavir propionate solvate.
14:
- The darunavir propionate solvate of claim 13, characterized by an X-Ray diffraction (XRD) pattern substantially in accordance with FIG. 1.
15-36:
- (canceled)
37:
- A process for preparation of amorphous darunavir, comprising the steps of:
- a) providing a solution of darunavir or a solvate thereof in an acid and a solvent;
- b) combining the solution of step a) with a solution of a base and water;
- and
- c) recovering the amorphous darunavir.
2 more elements
38:
- The process of claim 37, wherein the step a) comprises dissolving the darunavir or the solvate thereof or a pharmaceutically acceptable salt thereof in a solution comprising the acid, the solvent and a base.
39:
- The process of claim 37, wherein the acid is selected from the group consisting of acetic acid, propionic acid, formic acid, trifluoroacetic acid, butanoic acid, pentanoic acid, hexanoic acid, heptanoic acid, and the like and mixtures thereof.
40:
- (canceled)
41:
- The process of claim 38, wherein the base is selected form the group consisting of ammonia, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, and mixtures thereof.
42:
- (canceled)
43:
- The process of claim 37, wherein the solvent is selected from the group consisting of nitriles, alcohols such as methanol, ethanol, isopropanol, water, and mixtures thereof.
44:
- The process of claim 37, wherein the solvent is acetonitrile.
45:
- The process of claim 37, wherein the base in step b) is selected from the group consisting of ammonia, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, and mixtures thereof.
46-47:
- (canceled)
48:
- The process of claim 37, wherein the solution of step a) is provided at a temperature of about −20° C. to about 40° C.
49:
- The process of claim 37, wherein the step c) further comprises stirring the resultant solution at a temperature of about −10° C. to about 30° C.
50:
- Darunavir having a chemical purity of greater than about 99.8% as measured by HPLC.
51:
- The darunavir of claim 50 having less than about 0.1% by HPLC of one or more of its diastereomer impurities (R,S)-diastereomer, (S,S)-diastereomer, and (R,R)-diastereomer.
52:
- The darunavir of claim 50 substantially free of one or more of:
53:
- A pharmaceutical composition comprising amorphous darunavir or a solvate thereof or a pharmaceutically acceptable salt thereof, the amorphous darunavir made according to claim 37;
- and at least one pharmaceutically acceptable excipient.