Storage-stable ready-to-use injectable formulations of thiotepa
A stable, ready-to-use injectable solution including thiotepa and one or more pharmaceutically acceptable solvents, co-solvents, and/or solubilizing agents. Formulations retain at least 90% and as high as 99% of the purity of thiotepa as measured by HPLC after storage at 25° C./60% RH for a period of 7 days. Certain formulations retain at least 99% of the purity of thiotepa as measured by HPLC after storage for at least six months at 2-8° C.
1. A ready to use, pharmaceutically acceptable injectable liquid formulation comprising thiotepa or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable solvent or co-solvent, wherein the formulation retains at least 90% of the purity of thiotepa as measured by HPLC after storage at 25° C./60% relative humidity (RH) for a period of 7 days.
2. The formulation of claim 1 wherein the formulation retains at least 94% of the purity of thiotepa as measured by HPLC after storage at 25° C./60% RH for a period of 7 days.
3. The formulation of claim 1 wherein the formulation retains at least 99% of the purity of thiotepa as measured by HPLC after storage at 25° C./60% RH for a period of 7 days.
4. The formulation of claim 3 wherein the formulation retains at least 99% of the purity of thiotepa as measured by HPLC after storage for at least six months at 2-8° C.
5. The formulation of claim 1 comprising ethanol.
6. The formulation of claim 4 comprising ethanol.
7. The formulation of claim 1 comprising ethanol, propylene glycol and optionally one or more of a polymer and a solubilizing agent.
8. The formulation of claim 7 comprising 100 mg thiotepa, 1-10 ml ethanol and 0-5 ml propylene glycol.
9. The formulation of claim 8 comprising 10 ml ethanol and 0 ml propylene glycol.
10. The formulation of claim 7 comprising a polymer.
11. The formulation of claim 7 comprising a solubilizing agent.
12. The formulation of claim 7 comprising a polymer and a solubilizing agent.
13. The formulation of claim 1 consisting essentially of thiotepa and ethanol.
14. The formulation of claim 1 consisting of thiotepa and ethanol.
15. The formulation of claim 1 comprising ethanol, polyethylene glycol (PEG) and optionally one or more of a polymer and a solubilizing agent.
16. The formulation of claim 1 comprising ethanol, polyethylene glycol (PEG), a polymer and a solubilizing agent.
17. The formulation of claim 16 consisting essentially of ethanol, polyethylene glycol (PEG), a polymer, a solubilizing agent, and a pH adjusting component so that the pH of the formulation is from 7.5 to 8.5.
18. The formulation of claim 1 wherein the formulation has a concentration of thiotepa of about 10 mg thiotepa per ml of the total amount of the solvent and/or co-solvent.
19. The formulation of claim 2 wherein the formulation has a concentration of thiotepa of about 10 mg thiotepa per ml of the total amount of the solvent and/or co-solvent.
20. The formulation of claim 3 wherein the formulation has a concentration of thiotepa of about 10 mg thiotepa per ml of the total amount of the solvent and/or co-solvent.