OCULAR INFLAMMATION TREATMENT WITH STABILIZED DEXAMETHASONE
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 ocular inflammation 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 container that allows oxidation, 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) between 2.2% and 2.8% of a poloxamer;
iv) between 0% and 0.2% w/v of disodium edetate;
v) between 0% and 1% w/v of an electrolyte;
vi) between 0.1% and 0.5% w/v of sodium thiosulfate; and,
vii) water;
wherein the aqueous ophthalmic composition comprises a microsuspension comprising solid complexes of dexamethasone and γ-cyclodextrin.
2 . The method of claim 1 , wherein the composition comprises 1.5% w/v of dexamethasone.
3 . The method of claim 1 , wherein the composition comprises 14% w/v of γ-cyclodextrin.
4 . The method of claim 1 , wherein the composition comprises 2.5% of the poloxamer.
5 . The method of claim 1 , wherein the poloxamer is selected from the group consisting of poloxamer 101, poloxamer 105, poloxamer 108, poloxamer 122, poloxamer 123, poloxamer 124, poloxamer 181, poloxamer 182, poloxamer 183, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 212, poloxamer 215, poloxamer 217, poloxamer 231, poloxamer 234, poloxamer 235, poloxamer 237, poloxamer 238, poloxamer 282, poloxamer 284, poloxamer 288, poloxamer 331, poloxamer 333, poloxamer 334, poloxamer 335, poloxamer 338, poloxamer 401, poloxamer 402, poloxamer 403, poloxamer 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate.
6 . The method of claim 5 , wherein the poloxamer is poloxamer 407.
7 . The method of claim 1 , wherein the composition comprises 0.1% w/v of sodium edetate.
8 . The method of claim 1 , wherein the electrolyte is selected from the group consisting of sodium chloride and potassium chloride.
9 . The method of claim 8 , wherein the electrolyte is sodium chloride.
10 . The method of claim 9 , wherein the composition comprises 0.57 w/v of sodium chloride.
11 . The method of claim 1 , wherein the composition comprises 0.3% w/v of sodium thiosulfate which corresponds to water-free sodium thiosulfate.
12 . The method of claim 11 , wherein the sodium thiosulfate is the molar equivalent of sodium thiosulphate pentahydrate.
13 . The method of claim 1 , wherein the solid complexes comprise microparticles comprising a diameter D 50 ranging from about 1 μm to 10 μm.
14 . The method of claim 1 , wherein the inflammation is associated with ocular surgery.
15 . The method of claim 1 , wherein the ocular surgery is cataract surgery.
16 . The method of claim 1 , wherein the composition has a pH of between 4.5 and 6.
17 . The method of claim 1 , wherein the container is plastic.
18 . The method of claim 17 , wherein the container is low-density polyethylene (LDPE).
19 . A method of treating ocular inflammation 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 container that allows oxidation, the composition comprising:
i) 1.5% w/v of dexamethasone;
ii) 14 w/v of γ-cyclodextrin;
iii) 2.5% w/v of poloxamer 407;
iv) 0.1% w/v of disodium edetate;
v) 0.57% of sodium chloride; and,
vi) between 0.2% and 0.4% w/v of sodium thiosulfate; and,
vii) water;
wherein the aqueous ophthalmic composition comprises a microsuspension comprising solid complexes of dexamethasone and γ-cyclodextrin.
20 . The method of claim 19 , wherein the solid complexes comprise microparticles comprising a diameter D 50 ranging from about 1 μm to 10 μm.
21 . The method of claim 19 , wherein the composition comprises 0.3% w/v of sodium thiosulfate which corresponds to water-free sodium thiosulfate.
22 . The method of claim 21 , wherein the sodium thiosulfate is sodium thiosulphate pentahydrate.
23 . The method of claim 19 , that has a pH between 4.5 and 6.
24 . The method of claim 19 , wherein the inflammation is associated with ocular surgery.
25 . The method of claim 24 , wherein the ocular surgery is cataract surgery.
26 . The method of claim 25 , wherein the composition is administered as one drop a day.
27 . The method of claim 25 , wherein the composition is administered as two drops a day.
28 . The method of claim 25 , wherein the composition is administered for 14 days.
29 . The method of claim 19 , wherein the container is plastic.
30 . The method of claim 29 , wherein the container is low-density polyethylene (LDPE).