Process for preparing injectable Fosaprepitant Dimeglumine compositions having improved storage stability
Solid compositions having about 150 mg to about 245 mg Fosaprepitant that are stable after storage at about 25° C. for 6 months and processes for preparing solid Fosaprepitant compositions that are stable after long term storage at room temperature. The processes include freezing a Fosaprepitant solution in the primary packaging container at a first freezing temperature; applying vacuum at second temperature that is higher than the freezing temperature; fully stoppering the primary packaging container; and sealing the stoppered primary packaging container.
1. A process for preparing solid Fosaprepitant compositions that are stable after long term storage at room temperature, the process comprising the steps of:
dissolving Fosaprepitant active ingredient and excipients in water to form a Fosaprepitant solution;
filtering the Fosaprepitant solution;
filling the filtered solution into a primary packaging container;
partially stoppering the primary packaging container;
freezing the solution in the primary packaging container at a first freezing temperature;
applying vacuum at second temperature that is higher than the freezing temperature;
fully stoppering the primary packaging container; and
sealing the stoppered primary packaging container,
wherein the solution is held for up to about 72 hours before and/or after the step of filtering and prior to the step of filling.
2. The process of claim 1 , wherein the step of dissolving comprises dissolving the Fosaprepitant active ingredient and excipients in a first quantity of water and then subsequently adding a second quantity of water.
3. The process of claim 1 , wherein the primary packaging container is a vial and the step of partially stoppering comprises half stoppering the vial.
4. The process of claim 1 , wherein the freezing temperature is about −35° C. to about −55° C.
5. The process of claim 1 , wherein the second temperature is about −25° C. to about −5° C.
6. The process of claim 1 , wherein the vacuum is about 500 mT to about 100 mT.
7. The process of claim 1 , wherein after the step of the applying vacuum the process further comprises the step of secondary drying at a temperature greater than 0° C.
8. The process of claim 2 , wherein the excipients comprise a surface active agent.
9. The process of claim 8 , wherein the concentration of surface active agent in the Fosaprepitant solution is 10 mg/mL to 30 mg/mL.
10. The process of claim 1 , wherein the excipients comprise at least one of a chelating agent and a bulking agent.
11. The process of claim 1 , further comprising the step of adjusting the pH of the Fosaprepitant solution to be between pH 7 and 9.5.
12. The process of claim 1 , wherein the Fosaprepitant active ingredient is Fosaprepitant Dimeglumine.
13. The process of claim 1 , wherein the Fosaprepitant solution has a concentration of about 5 mg/mL to about 150 mg/mL Fosaprepitant.
14. The process of claim 2 , wherein the excipients comprise a bulking agent, surface active agent, and chelating agent.
15. The process of claim 2 , wherein the excipients consist of Polysorbate 80, lactose, povidone, and Disodium Edetate.
16. The process of claim 8 , wherein the surface active agent is Polysorbate 80.
17. A process for preparing solid Fosaprepitant compositions that are stable after long term storage at room temperature, the process comprising the steps of:
dissolving Fosaprepitant active ingredient and excipients in water to form a Fosaprepitant solution;
filtering the Fosaprepitant solution;
filling the filtered solution into a primary packaging container;
partially stoppering the primary packaging container;
freezing the solution in the primary packaging container at a first freezing temperature;
applying vacuum at second temperature that is higher than the freezing temperature;
fully stoppering the primary packaging container;
sealing the stoppered primary packaging container; and
storing the stoppered primary packaging container at about 25° C. for about 6 months, wherein the stored Fosaprepitant contains less than 2.5% Aprepitant.
18. The process of claim 17 , wherein the solution is held for up to about 72 hours before and/or after the step of filtering and prior to the step of filling.
19. The process of claim 17 , wherein the step of dissolving comprises dissolving the Fosaprepitant active ingredient and excipients in a first quantity of water and then subsequently adding a second quantity of water, the excipients consisting of Polysorbate 80, lactose, povidone, and Disodium Edetate.
20. The process of claim 19 , further comprising the step of adjusting the pH of the Fosaprepitant solution to about 7 to about 9.5.