Treatment of diabetic retinopathy
The present disclosure relates to a method for stabilizing the pH of an aqueous composition comprising a drug which is prone to oxidation, said method comprising the addition of an additive to prevent oxidation of the drug which is prone to oxidation. In particular, the present disclosure relates to a method for stabilizing the pH of an aqueous composition comprising a corticosteroid, said method comprising the addition of an additive to prevent oxidation of the corticosteroid. The present disclosure also relates to a composition comprising a corticosteroid and an additive to prevent oxidation of the corticosteroid.
1. A method of treating diabetic retinopathy in a human subject in need thereof, the method comprising topically administering to an affected eye of the subject an aqueous ophthalmic composition from a plastic container that allows oxidation of its contents, the composition comprising:
i) between 1% and 4% weight to volume (w/v) of dexamethasone
ii) between 5% and 25% w/v of γ-cyclodextrin;
iii) an anti-oxidation means for preventing the oxidation of dexamethasone in a manner that maintains a pH of between 4.5 and 6 for at least 6 months when stored at 25° C. and 40% relative humidity; and,
iv) water;
wherein the composition comprises a microsuspension comprising solid complexes of dexamethasone and γ-cyclodextrin.
2. The method of claim 1 , wherein the solid complexes comprise microparticles with a diameter D 50 ranging from about 1 μm to 10 μm.
3. The method of claim 1 , wherein the aqueous ophthalmic composition maintains a pH of between 4.5 and 6 for at least 9 months when stored at 25º C and 40% relative humidity.
4. The method of claim 1 , wherein the aqueous ophthalmic composition is capable of maintaining a pH with no more than a decrease of 0.5 in pH after being subject to 2 cycles of autoclaving comprising a heating cycle of 121 º C for 20 minutes in a glass vial under atmosphere, and wherein the composition is adjusted to a pH of between 4.9 and 5.1 before autoclaving.
5. The method of claim 1 , wherein the container is made of low-density polyethylene (LDPE).
6. The method of claim 1 , wherein the anti-oxidation means for preventing the oxidation of dexamethasone is sodium thiosulfate.
7. The method of claim 6 , wherein the sodium thiosulfate is sodium thiosulfate pentahydrate.
8. The method of claim 1 , wherein the aqueous ophthalmic composition further comprises between 2.2% and 2.8% w/v of a poloxamer.
9. The method of claim 8 , wherein the poloxamer is poloxamer 407.
10. The method of claim 1 , wherein the aqueous ophthalmic composition further comprises between 0% and 0.2% w/v of disodium edetate.
11. The method of claim 10 , wherein the aqueous ophthalmic composition comprises 0.1% w/v of disodium edetate.
12. The method of claim 1 , wherein the aqueous ophthalmic composition further comprises between 0% and 1% w/v of an electrolyte.
13. The method of claim 12 , wherein the electrolyte is selected from the group consisting of sodium chloride and potassium chloride.
14. The method of claim 13 , wherein the electrolyte is sodium chloride.
15. The method of claim 13 , wherein the electrolyte is 0.57% w/v of sodium chloride.
16. The method of claim 1 , wherein the aqueous ophthalmic composition comprises 1.5% w/v of dexamethasone.
17. The method of claim 1 , wherein the subject is vascular epithelial growth factor (VEGF) inhibitor naïve.
18. The method of claim 1 , wherein the subject has diabetic macular edema (DME).
19. The method of claim 1 , wherein the subject has retinal thickening due to diabetic macular edema (DME).