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 having pH about 5 to about 6 comprising:
(i) adalimumab;
(ii) buffer; and
(iii) stabilizer;
wherein the composition is free of both polyol and surfactant.
2. The composition of claim 1 , wherein the stabilizer is selected from the group consisting of an amino acid, a salt, EDTA and a metal ion.
3. The composition of claim 2 , wherein the amino acid is selected from the group consisting of glycine, arginine and combinations thereof.
4. The composition of claim 2 , wherein the salt is selected from the group consisting of sodium chloride and sodium sulfate.
5. The composition of claim 4 , wherein the salt is, or includes, sodium sulfate.
6. The composition of claim 1 , wherein the buffer contains no citrate and consists of histidine, succinate, or a combination thereof.
7. The composition of claim 1 , wherein the composition has a concentration of adalimumab of 30 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 6 , wherein histidine is the sole buffer in the composition; the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dosage; the composition has a concentration of adalimumab in the range of 30 to about 50 mg/ml; and the dosage contains about 10 to 80 mg of adalimumab.
10. The composition of claim 9 , wherein the dosage is about 40 mg and results in less pain upon administration to a subject in comparison to an adalimumab composition having a buffer that comprises citrate.
11. A buffered aqueous pharmaceutical composition having pH about 5 to about 6 comprising:
(i) adalimumab;
(ii) buffer consisting essentially of histidine, succinate, or both; and
(iii) a stabilizer, consisting essentially of:
(a) an amino acid selected from glycine, alanine, glutamate, arginine, methionine, and combinations thereof; or
(a) and (b), where (b) is sodium chloride, sodium sulfate or both;
wherein the composition is free of both polyol and surfactant.
12. The composition of claim 11 , comprising histidine as the sole buffer, and glycine.
13. The composition of claim 11 , comprising histidine as the sole buffer, and arginine.
14. The composition of claim 11 , wherein (b) is, or includes, sodium sulfate.
15. The composition of claim 11 , wherein (b) is, or includes, sodium chloride.
16. The composition of claim 11 , wherein the composition has a concentration of adalimumab of 30 to 50 mg/ml.
17. The composition of claim 16 , wherein the concentration of adalimumab is about 50 mg/ml.
18. The composition of claim 11 having osmolality of about 180 to 420 mOsM; wherein the composition is suitable for administration to a subject as a single dosage; the composition has a concentration of adalimumab in the range of 30 to about 50 mg/ml; and the dosage contains about 10 to 80 mg of adalimumab.
19. The composition of claim 18 , wherein the dosage is about 40 mg and results in less pain upon administration to a subject in comparison to an adalimumab composition having a buffer comprising citrate.
20. An aqueous buffered pharmaceutical composition having pH about 5 to about 6 comprising adalimumab and a citrate-free buffer, wherein the composition is free of both polyol and surfactant.
21. The composition of claim 20 , wherein the composition has a concentration of adalimumab of 30 to 50 mg/ml.
22. The composition of claim 21 , wherein the concentration of adalimumab is about 50 mg/ml.
23. The composition of claim 20 comprising: (i) adalimumab; (ii) buffer consisting solely of histidine, succinate, or combination thereof; and (iii) glycine, arginine or both.
24. The composition of claim 23 further comprising a salt selected from sodium chloride and sodium sulfate.
25. The composition of claim 23 having osmolality of about 180 to 420 mOsM; wherein the composition is suitable for administration to a subject as a single dosage; said composition having a concentration of adalimumab in the range of 30 to about 50 mg/ml; and the dosage contains about 10 to 80 mg of adalimumab.
26. The composition of claim 25 , wherein the concentration of adalimumab is about 50 mg/ml.
27. The composition of claim 25 , wherein the dosage is about 40 mg and results in less pain upon administration to a subject in comparison to an adalimumab composition having a buffer comprising citrate.