Stable aqueous formulations of adalimumab
The invention provides aqueous pharmaceutical adalimumab compositions suitable for long-term storage of adalimumab, methods of manufacture of these compositions, methods of administration, and kits containing same.
1. A buffered aqueous pharmaceutical composition comprising:
(i) adalimumab;
(ii) a buffer consisting solely of histidine; and
(iii) a polyol;
wherein the composition does not contain surfactant, and wherein the composition has a pH of about 5 to about 6, and is stable for one week at 40° C. or two weeks at 25° C.
2. The composition of claim 1 , wherein the polyol is mannitol.
3. The composition of claim 1 , wherein the polyol is sorbitol.
4. The composition of claim 1 , wherein the composition does not contain an amino acid other than histidine.
5. The composition of claim 1 , further comprising an amino acid selected from the group consisting of glycine, alanine, glutamate, arginine, and methionine, and combinations thereof.
6. The composition of claim 1 , further comprising sodium chloride or sodium sulfate at a concentration of up to 150 mM.
7. The composition of claim 1 , wherein the composition has a concentration of adalimumab of 30 mg/mL to 50 mg/mL.
8. The composition of claim 7 , wherein the concentration of adalimumab is about 50 mg/mL.
9. The composition of claim 1 having an osmolarity of about 180 mOsM to 420 mOsM; wherein the composition is suitable for administration to a subject as a single dosage; the composition has a concentration of adalimumab of 30 mg/mL to 50 mg/mL; and the dosage contains 10 mg to 80 mg of adalimumab.
10. The composition of claim 9 , further comprising sodium chloride at a concentration of up to 100 mM and wherein the polyol is sorbitol.
11. The composition of claim 9 , further comprising sodium chloride at a concentration of up to 100 mM and wherein the polyol is mannitol.
12. The composition of claim 9 , wherein the composition does not contain an amino acid other than histidine.
13. The composition of claim 9 , further comprising an amino acid selected from the group consisting of glycine, alanine, glutamate, arginine, and methionine, and combinations thereof.
14. The composition of claim 9 , further comprising sodium chloride or sodium sulfate at a concentration of up to 150 mM.
15. The composition of claim 9 , wherein the dosage is about 40 mg and has less tendency to cause pain upon administration to a subject in comparison to an adalimumab composition having a buffer that comprises citrate.
16. A buffered aqueous pharmaceutical composition comprising:
(i) adalimumab;
(ii) a buffer consisting solely of histidine; and
(iii) a stabilizer, consisting essentially of:
(a) an amino acid selected from the group consisting of glycine, alanine, glutamate, arginine, and methionine, and combinations thereof; and
(b) a polyol;
wherein the composition does not contain surfactant, and wherein the composition has a pH of about 5 to about 6, and is stable for one week at 40° C. or two weeks at 25° C.
17. The composition of claim 16 , wherein the amino acid selected from the group consisting of glycine, arginine, and methionine, and combinations thereof.
18. The composition of claim 16 , wherein the amino acid is glycine.
19. The composition of claim 18 , further comprising a salt, selected from sodium chloride and sodium sulfate, present at a concentration of up to 150 mM.
20. The composition of claim 16 , wherein the polyol is mannitol.
21. The composition of claim 16 , wherein the polyol is sorbitol.
22. The composition of claim 16 , wherein the composition has a concentration of adalimumab of 30 mg/mL to 50 mg/mL.
23. The composition of claim 22 , wherein the concentration of adalimumab is about 50 mg/mL.
24. The composition of claim 16 having an osmolarity of 180 mOsM to 420 mOsM; wherein the composition is suitable for administration to a subject as a single dosage; the composition has a concentration of adalimumab of 30 mg/mL to 50 mg/mL; and the dosage contains 10 mg to 80 mg of adalimumab.
25. The composition of claim 24 , wherein the concentration of adalimumab is about 50 mg/mL.
26. The composition of claim 24 , wherein the amino acid is glycine.
27. The composition of claim 26 , further comprising sodium chloride at a concentration of up to 100 mM and wherein the polyol is sorbitol.
28. The composition of claim 26 , further comprising sodium chloride present at a concentration of up to 100 mM and wherein the polyol is mannitol.
29. The composition of claim 28 , wherein the dosage is about 40 mg and has less tendency to cause pain upon administration to a subject in comparison to an adalimumab composition having a buffer that comprises citrate.