Bendamustine solution formulations
A ready to use or ready to dilute for use, stable liquid Bendamustine solution formed of 90 to about 200 mg/mL Bendamustine Hydrochloride or a hydrate form thereof, and a co-solvent consisting of 1% v/v to 12% v/v water and 88% v/v to 99% v/v N,N-Dimethylacetamide (DMA). The liquid Bendamustine solution is room-temperature stable for at least 90 days. Optionally, 0.01 to about 0.5 mg/mL antioxidant, preferably, butylated hydroxytoluene is included in the solution.
1. A ready to use or ready to dilute for use, stable liquid Bendamustine solution consisting essentially of:
about 90 to about 200 mg/mL Bendamustine Hydrochloride or a hydrate form thereof,
about 0.01 to about 0.5 mg/mL antioxidant, and
a co-solvent consisting of about 1% v/v to about 12% v/v water and about 88% v/v to about 99% v/v N,N-Dimethylacetamide (DMA),
the liquid Bendamustine solution being stable without the need for lyophilization, and wherein the formulation contains no less than about 98% of the amount of the Bendamustine Hydrochloride or a hydrate form thereof upon analysis by HPLC at initial testing and after 3 months at room temperature.
2. The Bendamustine solution of claim 1 , wherein the Bendamustine Hydrochloride or a hydrate form thereof is Bendamustine HCl monohydrate.
3. The Bendamustine solution of claim 1 , wherein the concentration of Bendamustine Hydrochloride or a hydrate form thereof is about 100 mg/m L.
4. The Bendamustine solution of claim 1 , wherein the cosolvent consists of about 2% v/v to about 6% v/v water.
5. The Bendamustine solution of claim 1 , wherein the cosolvent consists of 3% v/v water and 97% v/v DMA.
6. The Bendamustine solution of claim 1 , wherein the antioxidant concentration is about 0.05 mg/mL.
7. The Bendamustine solution of claim 1 , wherein the antioxidant concentration is about 0.018 mg/mL.
8. The Bendamustine solution of claim 1 , wherein the antioxidant concentration is about 0.5 mg/mL.
9. The Bendamustine solution of claim 1 , wherein the co-solvent is degassed with nitrogen.
10. The Bendamustine solution of claim 1 , wherein the antioxidant is butylated hydroxytoluene.
11. A pharmaceutically acceptable, sealed vial containing:
a ready to use or ready to dilute for use, stable Bendamustine solution consisting of:
about 10% w/v Bendamustine Hydrochloride or a hydrate thereof;
about 0.001 w/v to about 0.05% w/v antioxidant;
a cosolvent consisting of about 1% v/v to about 12% v/v water and about 88% v/v to about 99% v/v N,N-Dimethylacetamide (DMA); and
nitrogen;
wherein the Bendamustine solution is stable without the need for lypholization.
12. The pharmaceutically acceptable, sealed vial of claim 11 , wherein the antioxidant is butylated hydroxytoluene.
13. The pharmaceutically acceptable, sealed vial of claim 11 comprising 90-200 mg/mL Bendamustine Hydrochloride or a hydrate thereof.
14. A pharmaceutically acceptable, ready to use or ready to dilute for use, stable liquid Bendamustine composition comprising:
about 10% w/v Bendamustine Hydrochloride or a hydrate thereof; and
a cosolvent consisting of about 1% v/v to about 12% v/v water and about 88% v/v to about 99% v/v N,N-Dimethylacetamide (DMA),
wherein the composition is stable without the need for lyophilization, and substantially free of sodium chloride and/or polyols.
15. The liquid composition of claim 14 , further comprising a stabilizer.
16. The liquid composition of claim 15 , wherein the stabilizer is an antioxidant.
17. The liquid composition of claim 16 , wherein the antioxidant is butylated hydroxytoluene.
18. A method of treating leukemia or Hodgkin's disease by administering an effective amount of a ready to use or ready to dilute for use, stable liquid Bendamustine solution consisting essentially of:
about 90 to about 200 mg/mL Bendamustine Hydrochloride or a hydrate form thereof,
about 0.01 to about 0.5 mg/mL antioxidant, and
a co-solvent consisting of about 1% v/v to about 12% v/v water and about 88% v/v to about 99% v/v N,N-Dimethylacetamide (DMA),
the liquid Bendamustine solution being stable without the need for lyophilization, and wherein the formulation contains no less than about 98% of the amount of the Bendamustine Hydrochloride or a hydrate form thereof upon analysis by HPLC at initial testing and after 3 months at room temperature.
19. A ready to use or ready to dilute for use, stable liquid Bendamustine solution consisting essentially of:
about 90 to about 200 mg/mL Bendamustine Hydrochloride or a hydrate form thereof, and
a co-solvent consisting of about 1% v/v to about 12% v/v water and about 88% v/v to about 99% v/v N,N-Dimethylacetamide (DMA),
the liquid Bendamustine solution being stable without the need for lyophilization, and wherein the formulation contains no less than about 98% of the amount of the Bendamustine Hydrochloride or a hydrate form thereof upon analysis by HPLC at initial testing and after 3 months at room temperature.