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) a buffer consisting of solely histidine; and
(iii) a stabilizer, consisting essentially of an amino acid selected from glycine, arginine, methionine or combinations thereof;
wherein the composition does not contain polyol.
2. The composition of claim 1 , wherein the amino acid is glycine.
3. The composition of claim 1 , wherein the composition comprises sodium chloride or sodium sulfate at a concentration of up to 150 mM.
4. The composition of claim 1 having osmolality of 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 of 30 to 50 mg/ml; and the dosage contains 10 to 80 mg of adalimumab.
5. The composition of claim 4 comprising sodium chloride at a concentration of up to 100 mM and wherein the amino acid consists solely of glycine.
6. The composition of claim 5 , 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.
7. A buffered aqueous pharmaceutical composition having pH about 5 to about 6 comprising:
(i) adalimumab at a concentration of 30 to 50 mg/ml;
(ii) a buffer consisting solely of histidine; and
(iii) a stabilizer, consisting essentially of an amino acid selected from glycine, arginine, methionine or combinations thereof;
wherein the composition does not contain polyol.
8. The composition of claim 7 , wherein the concentration of adalimumab is about 50 mg/ml.
9. The composition of claim 7 , wherein the amino acid is glycine.
10. The composition of claim 9 further comprising a salt, selected from sodium chloride and sodium sulfate, present at a concentration of up to 150 mM.
11. The composition of claim 7 having osmolality of 180 to 420 mOsM; wherein the composition is suitable for administration to a subject as a single dosage; and the dosage contains 10 to 80 mg of adalimumab.
12. The composition of claim 11 , wherein the concentration of adalimumab is about 50 mg/ml.
13. The composition of claim 11 , wherein the dosage is about 40 mg.
14. The composition of claim 11 comprising sodium chloride present at a concentration of up to 100 mM; and wherein the amino acid is glycine.
15. The composition of claim 14 , 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.