PH STABILIZED TOPICAL OPHTHLAMIC COMPOSITIONS
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 . An aqueous ophthalmic composition in a container that allows oxidation of its contents comprising:
i) between 1 and 4% weight to volume (w/v) of dexamethasone
ii) between 5% and 25% w/v of γ-cyclodextrin;
iii) a 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 composition of claim 1 , wherein the solid complexes comprise microparticles with a diameter D 50 ranging from about 1 μm to 10 μm.
3 . The composition of claim 1 , wherein the composition maintains a pH of between 4.5 and 6 for at least 9 months when stored at 25° C. and 40% relative humidity.
4 . The composition of claim 1 , wherein the composition is capable of maintaining a pH with no more than a decrease of 1 in pH after being subject to 2 cycles of autoclaving under the conditions of Example 3.
5 . The composition of claim 1 , wherein the aqueous 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 under the conditions of Example 3.
6 . The composition of claim 1 , wherein the container is plastic.
7 . The composition of claim 6 , wherein the container is low-density polyethylene (LDPE).
8 . The composition of claim 1 , wherein the means for preventing the oxidation of dexamethasone is an antioxidant.
9 . The composition of claim 1 , wherein the means for preventing the oxidation of dexamethasone is an oxygen scavenger.
10 . The composition of claim 1 , wherein the means for preventing the oxidation of dexamethasone is sodium thiosulphate.
11 . The composition of claim 10 , wherein the sodium thiosulphate is sodium thiosulphate pentahydrate.
12 . The composition of claim 1 , wherein the means for preventing the oxidation of dexamethasone is L-methionine.
13 . The composition of claim 1 , wherein the means for preventing the oxidation of dexamethasone is 3,4-dihydoxybenzoic acid.
14 . The composition of claim 1 , wherein the means for preventing the oxidation of dexamethasone is selected from sodium citrate tribasic, DL-malic acid, (+)-sodium L-ascorbate, DL-tartaric acid, α-monothioclycerol, and butylated hydroxyanosiole.
15 . The composition of claim 1 , further comprising between 2.2% and 2.8% of a poloxamer.
16 . The composition of claim 1 , wherein the poloxamer is poloxamer 407.
17 . The composition of claim 1 , further comprising between 0% and 0.2% w/v of disodium edetate.
18 . The composition of claim 17 , wherein the composition comprises 0.1% w/v of disodium edetate.
19 . The composition of claim 1 , wherein the aqueous ophthalmic composition further comprises between 0% and 1% w/v of an electrolyte.
20 . The composition of claim 19 , wherein the electrolyte is selected from the group consisting of sodium chloride and potassium chloride.
21 . The composition of claim 20 , wherein the electrolyte is sodium chloride.
22 . The composition of claim 20 , wherein the electrolyte is 0.57% w/v of sodium chloride.
23 . The composition of claim 1 , wherein the composition comprises 1.5% w/v of dexamethasone.