Etanercept formulations stabilized with xylitol
View Patent ↗The invention provides stabilized aqueous pharmaceutical etanercept compositions suitable for long-term storage of etanercept, methods of manufacture of these compositions, methods of administration, and kits containing same.
1. A stabilized aqueous pharmaceutical composition comprising
a) etanercept,
b) buffer, and
c) stabilizer comprising 6 to 10 weight % xylitol,
wherein the composition has a pH of 6.0 to 6.6, or a pH within 10 percent of 6.0 and 6.6 and is free or essentially free of arginine.
2. The composition of claim 1 , wherein the pH is 6.3 or a pH within 10 percent of 6.3.
3. The composition of claim 1 , comprising 25 to 75 mg/mL of etanercept.
4. The composition of claim 3 , further comprising up to 100 mM NaCl and up to 5 wt. % sucrose.
5. The composition of claim 1 , comprising xylitol in an amount of 10 wt. % of the composition.
6. The composition of claim 1 , comprising 25 to 75 mg/mL of etanercept.
7. The composition of claim 6 , comprising 50 mg/mL or a concentration within 10 percent of 50 mg/ml of etanercept.
8. The composition of claim 7 , comprising 10 wt. % xylitol.
9. The composition of claim 7 , comprising 6 wt. % xylitol.
10. The composition of claim 6 , further comprising up to 100 mM NaCl and up to 5 wt. % sucrose.
11. The composition of claim 1 , further comprising one or more additional components selected from a tonicity modifier and an excipient.
12. The composition of claim 1 , further comprising up to 100 mM NaCl.
13. The composition of claim 1 , further comprising up to 5 wt. % sucrose.
14. A stabilized aqueous pharmaceutical composition comprising
a) 25 to 75 mg/mL of etanercept,
b) buffer, and
c) stabilizer comprising xylitol in an amount of 6 to 10 wt. % of the composition,
wherein the composition has a pH of 6.3 or a pH within 10 percent of 6.3, and is free or essentially free of arginine.
15. The composition of claim 14 , comprising 50 mg/mL or a concentration within 10 percent of 50 mg/ml of etanercept.
16. The composition of claim 15 , further comprising up to 100 mM NaCl and up to 5 wt. % sucrose.
17. The composition of claim 14 , comprising 6 wt. % xylitol.
18. The composition of claim 14 , comprising 50 mg/mL or a concentration within 10 percent of 50 mg/ml of etanercept and 10 wt. % xylitol.
19. The composition of claim 14 , comprising 50 mg/mL or a concentration within 10 percent of 50 mg/ml of etanercept and 6 wt. % xylitol.
20. The composition of claim 14 , further comprising one or more additional components selected from a tonicity modifier and an excipient.
21. The composition of claim 14 , further comprising up to 100 mM NaCl.
22. The composition of claim 14 , further comprising up to 5 wt. % sucrose.
23. The composition of claim 14 , further comprising up to 100 mM NaCl and up to 5 wt. % sucrose.
24. The composition of claim 23 , wherein the composition has osmolality of 180 to 420 milliosmoles or an osmolality within 10 percent of 180 to 420 milliosmoles; the composition is suitable for administration to a subject as a single dose; and the dose contains 10-80 mg/dose etanercept.