Pharmaceutical formulation
Disclosed are aqueous pharmaceutical compositions which provide sustained released delivery of corticosteroid compounds. The pharmaceutical composition comprises an insoluble corticosteroid; a soluble corticosteroid; and at least one viscosity enhancing agent. Also provided are methods for using the pharmaceutical compositions in an epidural injection, intra-articular injection, intra-lesional injection, or an intra-ocular injection.
1. An aqueous pharmaceutical composition comprising
an insoluble corticosteroid;
a soluble corticosteroid; and
at least one viscosity enhancing agent;
wherein the at least one viscosity enhancing agent is sodium hyaluronate or hyaluronic acid and the insoluble corticosteroid and soluble corticosteroid are selected from the group consisting of salts and esters of dexamethasone,
wherein the molecular weight of at least one viscosity enhancing agent is between 1.0 MDa and 2.5 MDa; and
wherein the concentration of the at least one viscosity enhancing agent is between 1.0% w/v and 1.5% w/v.
2. The aqueous pharmaceutical composition of claim 1 , wherein the soluble corticosteroid is dexamethasone sodium phosphate and the insoluble corticosteroid is dexamethasone acetate.
3. The aqueous pharmaceutical composition of claim 1 , wherein the at least one viscosity enhancing agent is sodium hyaluronate.
4. The aqueous pharmaceutical composition of claim 1 , wherein the at least one viscosity enhancing agent is hyaluronic acid.
5. The aqueous pharmaceutical composition of claim 1 , wherein the weight ratio or molar ratio of soluble corticosteroid to insoluble corticosteroid ranges from about 1:4 to 4:1.
6. The aqueous pharmaceutical composition of claim 5 , wherein the weight ratio or molar ratio of soluble corticosteroid to insoluble corticosteroid is 1:4.
7. The aqueous pharmaceutical composition of claim 1 , wherein the molecular weight of the at least one viscosity enhancing agent is between 1.0 MDa and 2.0 MDa.
8. The aqueous pharmaceutical composition of claim 1 , wherein the molecular weight of the at least one viscosity enhancing agent is between 1.2 MDa and 2.0 MDa.
9. The aqueous pharmaceutical composition of claim 1 , wherein the molecular weight of the at least one viscosity enhancing agent is between 1.2 MDa and 1.8 MDa.
10. The aqueous pharmaceutical composition of claim 1 , wherein the molecular weight of the at least one viscosity enhancing agent is about 1.56 MDa.
11. The aqueous pharmaceutical composition of claim 1 , wherein the concentration of the at least one viscosity enhancing agent is about 1.25% w/v.
12. The aqueous pharmaceutical composition of claim 1 , wherein the soluble corticosteroid is dexamethasone sodium phosphate, the insoluble corticosteroid is dexamethasone acetate, and the at least one viscosity enhancing agent is sodium hyaluronate,
wherein the molecular weight of the sodium hyaluronate is between 1.0 MDa and 2.0 MDa, and the concentration of the sodium hyaluronate is about 1.25% w/v.
13. The aqueous pharmaceutical composition of claim 12 , wherein the weight ratio or molar ratio of soluble corticosteroid to insoluble corticosteroid ranges from about 1:4 to 4:1.
14. The aqueous pharmaceutical composition of claim 13 , wherein the weight ratio or molar ratio of soluble corticosteroid to insoluble corticosteroid is 1:4.
15. The aqueous pharmaceutical composition of claim 1 , wherein the insoluble corticosteroid and soluble corticosteroid selected from the group consisting of salts and esters of dexamethasone are present at a weight equivalent to achieve a dexamethasone concentration of about 5 mg/mL.
16. The aqueous pharmaceutical composition of claim 1 , wherein the insoluble corticosteroid has an average particle size of less than 10 μm.
17. The aqueous pharmaceutical composition of claim 1 , further comprising a preservative and/or an anesthetic.
18. The aqueous pharmaceutical composition of claim 1 , wherein the aqueous pharmaceutical composition has a viscosity of between 1 kcP and 200 kcP.
19. The aqueous pharmaceutical composition of claim 1 , wherein the aqueous pharmaceutical composition has a viscosity of between 10 kcP and 100 kcP.
20. The aqueous pharmaceutical composition of claim 1 , wherein the aqueous pharmaceutical composition is injectable.
21. A method for treating inflammation and/or pain in an individual in need thereof, comprising injecting the aqueous pharmaceutical composition of claim 1 into the individual in need thereof.
22. The method of claim 21 , wherein the aqueous pharmaceutical composition is injected into an intralesional or intra-articular space.
23. The method of claim 21 , wherein less than 20 N of force is used to inject the aqueous pharmaceutical composition.
24. The method of claim 21 , wherein less than 27 N of force is used to inject the aqueous pharmaceutical composition.
25. The method of claim 21 , wherein the individual in need thereof is injected with the aqueous pharmaceutical composition once every 4 to 24 weeks.
26. The method of claim 21 , wherein the soluble corticosteroid is dexamethasone sodium phosphate, the insoluble corticosteroid is dexamethasone acetate, and the at least one viscosity enhancing agent is sodium hyaluronate,
wherein the molecular weight of the sodium hyaluronate is between 1.0 MDa and 2.0 MDa, and the concentration of the sodium hyaluronate is about 1.25% w/v.
27. The method of claim 21 , wherein the weight ratio or molar ratio of soluble corticosteroid to insoluble corticosteroid ranges from about 1:4 to 4:1.
28. The method of claim 27 , wherein the weight ratio or molar ratio of soluble corticosteroid to insoluble corticosteroid is 1:4.
29. The method of claim 21 , wherein the insoluble corticosteroid and soluble corticosteroid selected from the group consisting of salts and esters of dexamethasone are present at a weight equivalent to achieve a dexamethasone concentration of about 5 mg/mL.
30. The method of claim 21 , wherein the insoluble corticosteroid has an average particle size of less than 10 μm.
31. The method of claim 21 , wherein the soluble corticosteroid is dexamethasone sodium phosphate and the insoluble corticosteroid is dexamethasone acetate.
32. The method of claim 21 , wherein the at least one viscosity enhancing agent is sodium hyaluronate.
33. The method of claim 21 , wherein the at least one viscosity enhancing agent is hyaluronic acid.
34. The method of claim 21 , wherein the molecular weight of the at least one viscosity enhancing agent is between 1.0 MDa and 2.0 MDa.
35. The method of claim 21 , wherein the concentration of the at least one viscosity enhancing agent is about 1.25% w/v.
36. The method of claim 21 , wherein the aqueous pharmaceutical composition has a viscosity of between 1 kcP and 200 kcP.
37. The method of claim 21 , wherein the aqueous pharmaceutical composition has a viscosity of between 10 kcP and 100 kcP.
38. A syringe comprising the aqueous pharmaceutical composition of claim 1 .