Stable aqueous formulations of adalimumab
View Patent ↗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 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, 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 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; the dosage contains 10 to 80 mg of adalimumab; and wherein the composition optionally comprises phosphate solely as an added stabilizer, and not as a buffer, such that the composition has pH of about 5 to about 6 without phosphate.
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 comprising:
(i) adalimumab at a concentration of 40 mg/ml;
(ii) a buffer consisting solely of histidine; and
(iii) a stabilizer, consisting essentially of an amino acid selected from the group consisting of glycine, arginine, methionine and combination thereof; and wherein the composition does not contain polyol, has a pH of about 5 to about 6, and is stable for one week at 40° C. or two weeks at 25° C.
8. The composition of claim 7 wherein the amino acid is glycine.
9. The composition of claim 8 , further comprising a salt, selected from sodium chloride and sodium sulfate, present at a concentration of up to 150 mM.
10. 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; the composition has a concentration of adalimumab of 30 to 50 mg/ml; the dosage contains 10 to 80 mg of adalimumab; and wherein the composition optionally may contain phosphate solely as an added stabilizer, and not as a buffer, such that the composition has pH of about 5 to about 6 without phosphate.
11. The composition of claim 10 comprising sodium chloride present at a concentration of up to 100 mM; and wherein the amino acid is glycine.
12. The composition of claim 11 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.