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 stable aqueous pharmaceutical composition comprising:
a) about 30 mg/mL to about 50 mg/mL adalimumab;
b) at least one of succinate, histidine, phosphate, tartrate, maleate, and citrate buffer;
c) about 65 mM to about 240 mM sorbitol; and
d) about 0.01 wt % to about 0.2 wt % of a surfactant,
wherein i) the buffer does not comprise a combination of citrate and phosphate, ii) the composition is free of sodium chloride, and iii) the composition has a pH of about 5 to about 5.5, and is stable at 40° C. for one week or at 25° C. for two weeks.
2. The composition of claim 1 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
3. The composition of claim 1 , wherein the pH is about 5.2.
4. The composition of claim 3 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
5. A stable aqueous pharmaceutical composition comprising:
a) about 30 mg/mL to about 50 mg/mL adalimumab;
b) at least one of succinate, histidine, phosphate, tartrate, maleate, and citrate buffer;
c) about 65 mM to about 240 mM sorbitol; and
d) about 0.01 wt % to about 0.2 wt % of polysorbate 20,
wherein i) the buffer does not comprise a combination of citrate and phosphate, ii) the composition is free of sodium chloride, and iii) the composition has a pH of about 5 to about 5.5, and is stable at 40° C. for one week or at 25° C. for two weeks.
6. The composition of claim 5 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
7. The composition of claim 5 , wherein the pH is about 5.2.
8. The composition of claim 7 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
9. A stable aqueous pharmaceutical composition comprising:
a) about 30 mg/mL to about 50 mg/mL adalimumab;
b) histidine and citrate buffers;
c) about 65 mM to about 240 mM sorbitol; and
d) about 0.01 wt % to about 0.2 wt % of a surfactant,
wherein i) the buffer does not comprise a combination of citrate and phosphate; ii) the composition is free of sodium chloride, and iii) the composition has a pH of about 5 to about 5.5, and is stable at 40° C. for one week or at 25° C. for two weeks.
10. The composition of claim 9 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
11. The composition of claim 9 , wherein the pH is about 5.2.
12. The composition of claim 11 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
13. A stable aqueous pharmaceutical composition comprising:
a) about 30 mg/mL to about 50 mg/mL adalimumab;
b) histidine and citrate buffers;
c) about 65 mM to about 240 mM sorbitol; and
d) about 0.01 wt % to about 0.2 wt % of polysorbate 20,
wherein i) the buffer does not comprise a combination of citrate and phosphate; ii) the composition is free of sodium chloride, and iii) the composition has a pH of about 5 to about 5.5, and is stable at 40° C. for one week or at 25° C. for two weeks.
14. The composition of claim 13 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.
15. The composition of claim 13 , wherein the pH is about 5.2.
16. The composition of claim 15 , wherein the composition has osmolality of about 180 to 420 mOsM; the composition is suitable for administration to a subject as a single dose; and the dose contains about 40 mg of adalimumab.