Process for the preparation of gabapentin form-II
AssigneeMatrix Laboratories Limited
InventorsSatyanarayana Chava, Seeta Gorantla, Venkata Indukurl
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Abstract
The present invention relates to a new industrial feasible process for the preparation of Gabapentin Form-II via a novel intermediate Gabapentin hemisulphate hemihydrate with out forming Gabapentin Form-III by neutralizing the Gabapentin hemisulphate hemihydrate solution with a base at higher temperatures followed by cooling to yield Gabapentin Form II with sulphate ions less than 100 ppm with respect to Gabapentin.
Claims18
A process for the preparation of Gabapentin Form-II comprising the steps of:
- reacting 1,1-cyclohexane di acetic acid mono amide with an alkali hypo halite solution at a temperature of about −10° C. to about 5° C., followed by acidification with sulphuric acid in presence of a first organic solvent;
- extracting the formed sulphate salt into an organic layer with a second organic solvent;
- separating the organic layer, followed by drying the layer over dehydrating agents;
- adding an ante solvent to precipitate the formed hemisulphate hemihydrate salt followed by its isolation;
- dissolving the hemisulphate hemihydrate salt in a short chain alcohol and
- separating an insolubles from the salt solution to form a salt solution filtrate;
- neutralizing the filtrate with a base at temperature of about 70° C. to liberate the free amino acid;
- isolating the liberated free amino acid by cooling, leaving formed byproduct base-salt in the mother liquor/solvent;
- separating the formed Gabapentin Form-II followed by purification by slurrying in ethanol at temperature of about 60° C.-70° C.;
- and
- recovering the final product by filtering and drying to obtain Gabapentin Form-II having sulphate ions less than 100 ppm with respect to Gabapentin.
Crystalline Gabapentin hemisulphate hemihydrate characterized by powder x-ray diffraction peaks at 2-theta 6.8, 13.7, 17,0, 18.0, 20.2, 20.6, 24,2, 24.6, 26.2, 26.8, 27.7, 29.9, 30,8, 34.0, and 34.7 degrees.
Crystalline Gabapentin hemisulphate hemihydrate characterized by infra-red absorptions having peaks at 686, 757, 901, 917, 986, 1127, 1142, 1200, 1282, 1315, 1430, 1462, 1525, 1580 and 1714 cm−1.
A process for the preparation of Gabapentin hemisulphate hemihydrate comprising the steps of:
- reacting 1,1-cyclohexane di acetic acid mono amide with an alkali hypo halite solution at temperature of about −10° C. to about 5° C., followed by acidification with sulphuric acid in presence of a first is organic solvent;
- extracting the formed sulphate salt into an organic layer with a second organic solvent;
- separating the organic layer, and drying it over dehydrating agents;
- adding an ante solvent to the organic layer to precipitate a hemisulphate hemihydrate salt followed by its isolation;
- and
- isolating and drying Gabapentin hemisulphate hemihydrate.
(canceled)
Dependencies are inferred from the claim text.