Stable liquid formulations of nitrogen mustards
AssigneeColdstream Laboratories Inc.
InventorsSundar Neelakantan, Eric W. Smart, Charles Reichel
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Abstract
Described are stable liquid formulations of nitrogen mustards. The nitrogen mustard includes mechlorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil, uramustine, thiotepa and combinations thereof. The formulation includes a non-aqueous liquid having at least a first solvent either individually or in combination with one or more additional solvents. The formulation further includes an antioxidant, an organic acid, and a source of chloride ions.
Claims20
A stable liquid formulation of a nitrogen mustard comprising:
- a nitrogen mustard in an amount of about 0.1% w/w to about 10% w/w of the formulation, wherein the nitrogen mustard is selected from the group consisting of mechlorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil, uramustine, thiotepa and combinations thereof;
- a non-aqueous liquid in an amount of about 45% w/w to about 98% w/w of the formulation, the non-aqueous liquid comprising a first solvent;
- an antioxidant in an amount of about 0.01% w/w to about 1% w/w of the formulation;
- an organic acid in an amount of about 0.02% w/w to about 1.5% w/w of the formulation;
- and
- a source of chloride ions in an amount of about 0.05% w/w to about 15% w/w of the formulation.
A stable liquid formulation of a nitrogen mustard comprising:
- a nitrogen mustard in an amount of about 0.1% w/w to about 10% w/w of the formulation, wherein the nitrogen mustard is selected from the group consisting of mechlorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil, uramustine, thiotepa and combinations thereof;
- a non-aqueous liquid in an amount of about 45% w/w to about 98% w/w of the formulation, the non-aqueous liquid comprising a first solvent;
- an organic acid in an amount sufficient to maintain the nitrogen mustard in a protonated state and to maintain the pH of the formulation;
- an antioxidant;
- and
- a source of chloride ions,
- wherein the antioxidant and the source of chloride ions are present, in combination, at a concentration effective to prevent the formation of greater than 5% impurities when the formulation is stored at about 25 degrees Celsius for 2 weeks.
A method of improving the stability of a nitrogen mustard comprising:
- mixing a nitrogen mustard selected from the group consisting of mechlorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil, uramustine, thiotepa and combinations thereof with a non-aqueous liquid in an amount of about 45% w/w to about 98% w/w of the formulation, the non-aqueous liquid comprising a first solvent,
- an organic acid in an amount sufficient to maintain the nitrogen mustard in a protonated state and to maintain the pH of the formulation;
- an antioxidant;
- and
- a source of chloride ions,
- wherein the antioxidant and the source of chloride ions are provided, in combination, at a concentration effective to prevent the formation of greater than 5% impurities when the formulation is stored at about 25 degrees Celsius for 2 weeks.
Dependencies are inferred from the claim text.