LFA-1 INHIBITOR FORMULATIONS
The present invention provides formulations, methods and kits for the treatment of dry eye diseases. In particular, stabilized pharmaceutical compositions comprising the compound of Formula 1 are described herein for a variety of uses including the treatment of dry eye syndrome. In one aspect, methods and ingredients for improving the stability of compositions of the compound of Formula 1 are described.
1 .- 52 . (canceled)
53 . A method of treating disease in a subject in need thereof comprising the step of administering an effective amount of a composition to said subject, wherein the composition comprises a compound of Formula 1:
or a salt thereof,
a pharmaceutically acceptable carrier, and
a thiosulfate salt,
wherein the composition has less than about 1% of total degradation products of the compound of Formula 1 when stored at a temperature of about 40° C. for a period of at least one month.
54 . The method of claim 53 , wherein the disease is an eye disease.
55 . The method of claim 60 , wherein the dry eye disease is secondary to presumed ocular surface inflammation.
56 . The method of claim 54 , wherein said administering comprises topical administration to the eye.
57 . The method of claim 56 , wherein said composition is administered in the form of eye drops.
58 .- 59 . (canceled)
60 . The method of claim 54 , wherein the eye disease is dry eye syndrome.
61 . The method of claim 53 , wherein the composition comprises thiosulfate salt in an amount of about 0.01% to about 0.5% w/v.
62 . The method of claim 61 , wherein the thiosulfate salt is present in an amount of about 0.3% w/v.
63 . The method of claim 53 , wherein the thiosulfate salt in the composition is sodium thiosulfate.
64 . The method of claim 53 , wherein the composition is buffered to a pH of about 6.0 to about 8.5.
65 . The method of claim 53 , wherein the compound of Formula 1 is present in the composition in an amount of about 1% to about 5% w/v.
66 . The method of claim 65 , wherein the compound of Formula 1 is present in an amount of about 5% w/v.
67 . The method of claim 53 , wherein the composition exhibits less than about 1% of total degradation products of the compound of Formula 1 upon storage at a temperature of about 40° C. for a time period selected from the group consisting of 2 months, 3 months, 4 months, 5 months, and 6 months.
68 . The method of claim 53 , wherein the composition further comprises a sparged nitrogen gas.
69 . The method of claim 53 , wherein the composition comprises:
about 5% w/v of the compound of Formula 1;
about 0.3% w/v thiosulfate salt;
sodium chloride; and
sodium phosphate, and
wherein the composition has a pH of about 7.0 to about 8.0.
70 . The method of claim 69 , wherein the sodium phosphate is dibasic sodium phosphate.
71 . A method of treating a disease in a subject in need thereof, comprising the step of administering an effective amount of a composition to said subject, wherein the composition comprises:
4 to 10 w/v % compound of Formula 1:
or a salt thereof; and
0.2 to 0.4% antioxidant, the antioxidant being sodium thiosulfate;
wherein the composition is an aqueous solution with the compound of Formula 1 dissolved therein, and
wherein the composition is suitable for topical administration to the eye, and wherein the disease is an eye disease.
72 . The method of claim 71 , wherein the composition comprises:
about 5 w/v % compound of Formula 1 or a salt thereof;
about 0.3% w/v of sodium thiosulfate;
sodium phosphate for buffering the compositions at a pH of 6.0 to 8.0; and
sodium chloride for providing isotonicity to the composition.
73 . The method of claim 72 , wherein the composition is buffered to a pH of about 7.5.
74 . The method of claim 71 , wherein the eye disease is dry eye disease.
75 . The method of claim 74 , wherein the dry eye disease is secondary to presumed ocular surface inflammation.