Aztreonam β polymorph with very low residual solvent content
AssigneeTEVA Gyógyszergyár Zártkörüen Müködö Részvénytársaság
InventorsViktor Gyollai, Csaba Szabo, Claude Singer, Ehud Amir
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Abstract
The invention relates to the β polymorph of Aztreonam, which contains less than 2.5% by weight residual solvent and to a process of making said polymorph. In the process of the invention, a polymorph of Aztreonam is dissolved in an absolute C1-6 alcohol in the presence of a base to form a solution, an acid is added to the solution, and the solution is stirred efficiently.
Claims46
Crystalline, anhydrous β polymorph of Aztreonam having about 0.5% or less by weight of residual solvent.
A method for making the crystalline, anhydrous β polymorph of Aztreonam, comprising:
- (a) dissolving a polymorph of Aztreonam in an absolute C1-6 alcohol at a temperature of between about −60° C. to about 5° C. in the presence of a base to form a clear solution;
- (b) adding acid to the solution formed in (a);
- (c) stirring the solution efficiently;
- and
- (d) recovering the β polymorph of Aztreonam.
A method for making the crystalline, anhydrous β polymorph of Aztreonam having less than 2.5% by weight residual solvent, comprising
- (a) dissolving a polymorph of Aztreonam in an absolute C1-6 alcohol, in the presence of a base, at a temperature sufficient to achieve crystallization of the β polymorph within about 16 to about 24 hours;
- (b) adding acid to the solution formed in (a);
- (c) seeding the solution with the β polymorph of Aztreonam;
- and
- (d) stirring the solution efficiently for a time sufficient to precipitate the β polymorph of Aztreonam.
A method for making the crystalline, anhydrous β polymorph of Aztreonam,
- comprising:
- (a) dissolving a polymorph of Aztreonam in an absolute C1-6 alcohol at a temperature of between about −60° C. to about 5° C. in the presence of a base to form a clear solution;
- (b) adding acid to the solution formed in (a);
- (c) stirring the solution efficiently;
- (d) seeding with the β polymorph of Aztreonam;
- (e) forming a slurry with ethanol;
- and
- (d) recovering the β polymorph of Aztreonam.
Crystalline, anhydrous β polymorph of Aztreonam, containing ethanol, wherein the ethanol is present in an amount of 1% or less by weight.
Crystalline, anhydrous β polymorph of Aztreonam, containing methanol, wherein the methanol is present in an amount of about 0.5% or less by weight.
Dependencies are inferred from the claim text.