Syringe containing 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 syringe having a single dose of an aqueous pharmaceutical composition wherein the aqueous pharmaceutical composition comprises:
(i) adalimumab;
(ii) a buffer; and
(iii) a stabilizer;
wherein the composition is free of 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 syringe 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 syringe of claim 2 , wherein the amino acid is selected from the group consisting of glycine, arginine, and a combination thereof.
4. The syringe of claim 2 , wherein the salt is selected from the group consisting of sodium chloride and sodium sulfate.
5. The syringe of claim 4 , wherein the salt is, or includes, sodium sulfate.
6. The syringe of claim 5 , wherein the buffer contains no citrate and consists of histidine, succinate, or a combination thereof; and wherein the composition may further optionally include (i) phosphate acting as a stabilizer and not as a buffer, so that the composition is at pH about 5 to about 6 without phosphate or (ii) PS80 surfactant; or both.
7. The syringe 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 dose; the composition has a concentration of adalimumab in the range of 30 to about 50 mg/mL; and the dose contains about 10 to 80 mg of adalimumab.
8. The syringe of claim 7 , wherein the dose 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.
9. A syringe having a single dose of an aqueous pharmaceutical composition wherein the aqueous pharmaceutical composition has a pH of about 5 to about 6 and comprises:
(i) adalimumab;
(ii) a buffer, free of citrate, and consisting essentially of histidine, succinate, or both; and
(iii) a stabilizer consisting essentially of:
(a) glycine, arginine, or both; or
(a) and (b); where (b) is sodium chloride, sodium sulfate, or both;
wherein the composition is free of polyol, and is stable for one week at 40° C. or two weeks at 25° C.
10. The syringe of claim 9 comprising histidine as the sole buffer, and glycine.
11. The syringe of claim 9 comprising histidine as the sole buffer, and arginine.
12. The syringe of claim 9 , wherein (b) is, or includes, sodium sulfate.
13. The syringe of claim 9 further comprising phosphate acting as a stabilizer and not as a buffer so that the composition is at a pH from about 5 to about 6 without phosphate; and, optionally, a surfactant.
14. The syringe of claim 9 having osmolality of about 180 to 420 mOsM; wherein the composition is suitable for administration to a subject as a single dose; the composition has a concentration of adalimumab in the range of 30 to about 50 mg/mL; and the dose contains about 10 to 80 mg of adalimumab.
15. The syringe of claim 14 , wherein the dose 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.
16. A syringe having a single dose of an aqueous pharmaceutical composition wherein the aqueous pharmaceutical composition has a pH of about 5 to about 6 and comprises adalimumab and a citrate-free buffer, and wherein the composition is free of 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.
17. The syringe of claim 16 comprising: (i) adalimumab; (ii) buffer consisting solely of histidine, succinate, or combination thereof; and (iii) glycine, arginine, or both.
18. The syringe of claim 17 further comprising phosphate acting as a stabilizer and not as a buffer.
19. The syringe of claim 17 further comprising a salt selected from sodium chloride and sodium sulfate.
20. The syringe of claim 17 having osmolality of about 180 to 420 mOsM; wherein the composition is suitable for administration to a subject as a single dose; the composition having a concentration of adalimumab in the range of 30 to about 50 mg/mL; the dose containing about 40 mg of adalimumab and resulting in less pain upon administration to a subject in comparison to an adalimumab composition having a buffer that comprises citrate.