Hydralazine compositions and methods
A sterile, ready-to-use pharmaceutical composition having hydralazine and/or a salt thereof at a concentration of less than about 20 mg/mL and a solvent comprising an organic co-solvent, wherein the hydralazine and/or salt thereof and the organic co-solvent are provided at a first weight ratio sufficient for the hydralazine and/or salt thereof to have a change in concentration of no more than about 10% after 2 months of storage at 60° C. Also described are methods of making and using the composition.
1. A sterile, ready-to-use pharmaceutical composition comprising:
hydralazine and/or a salt thereof at a concentration of about 10 mg/mL, and
a solvent comprising a co-solvent, wherein the solvent comprises water and the co-solvent comprises propylene glycol,
wherein the co-solvent and the hydralazine and/or salt thereof are provided at a weight ratio of no more than about 7.5:1, and wherein the hydralazine and/or salt thereof has a change in concentration of no more than about 10% after 2 months of storage at 60° C.
2. The composition of claim 1 , wherein the weight ratio is no more than about 6:1.
3. The composition of claim 1 , wherein the co-solvent is provided at a concentration of about 5% v/v.
4. The composition of claim 1 , further comprising a buffer.
5. The composition of claim 4 , wherein the buffer comprises a citrate buffer, a tartrate buffer, and/or an acetate buffer.
6. The composition of claim 1 , further comprising a chelating agent.
7. The composition of claim 6 , wherein the chelating agent is selected from the group consisting of ethylenediaminetetraacetic acid, ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid, and penta(carboxymethyl)diethylenetriamine.
8. The composition of claim 1 , further comprising a tonicity agent.
9. The composition of claim 8 , wherein the tonicity agent comprises a pharmaceutically acceptable salt.
10. The composition of claim 1 , wherein the composition is provided in a bag.
11. The composition of claim 1 , wherein the composition is provided in a bottle.
12. The composition of claim 1 , wherein the hydralazine and/or salt thereof has a change in concentration of no more than about 8% after 2 months of storage at 60° C.
13. A pre-filled syringe comprising a sterile, ready-to-use pharmaceutical composition, the composition comprising:
hydralazine and/or a salt thereof at a concentration of about 10 mg/mL, and
a solvent comprising a co-solvent, wherein the solvent comprises water and the co-solvent comprises propylene glycol,
wherein the co-solvent and the hydralazine and/or salt thereof are provided at a weight ratio of no more than about 7.5:1, and wherein the hydralazine and/or salt thereof has a change in concentration of no more than about 10% after 2 months of storage at 60° C.
14. The pre-filled syringe of claim 13 , wherein the pre-filled syringe comprises between about 1 mL and 5 mL of the composition.
15. The pre-filled syringe of claim 13 , wherein the weight ratio is no more than about 6:1.
16. The pre-filled syringe of claim 13 , wherein the co-solvent is provided at a concentration of about 5% v/v.
17. A method of treating hypertension comprising administering to a subject in need thereof a sterile, ready-to-use pharmaceutical composition, the composition comprising:
hydralazine and/or a salt thereof at a concentration of about 10 mg/mL, and
a solvent comprising a co-solvent, wherein the solvent comprises water and the co-solvent comprises propylene glycol,
wherein the co-solvent and the hydralazine and/or salt thereof are provided at a weight ratio of no more than about 7.5:1, and wherein the hydralazine and/or salt thereof has a change in concentration of no more than about 10% after 2 months of storage at 60° C.
18. The method of claim 17 , wherein the administering is performed by direct injection from a pre-filled syringe.