LFA-1 inhibitor formulations
View Patent ↗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. A composition comprising 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.
2. The composition of claim 1 , wherein the pharmaceutically acceptable carrier is an aqueous carrier.
3. The composition of claim 2 , wherein the thiosulfate salt is present in an amount of about 0.01% to about 0.5% w/v.
4. The composition of claim 2 , wherein the thiosulfate salt is present in an amount of about 0.3% w/v.
5. The composition of claim 3 , wherein the thiosulfate salt is sodium thiosulfate.
6. The composition of claim 5 , wherein the composition is buffered to a pH of about 6.0 to about 8.5.
7. The composition of claim 6 , wherein the compound of Formula 1 is present in an amount of about 1% to about 5% w/v.
8. The composition of claim 7 , wherein the compound of Formula 1 is present in an amount of about 5% w/v.
9. The composition of claim 8 , 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.
10. The composition of claim 8 , further comprising a sparged nitrogen gas.
11. The composition of claim 1 , comprising:
about 5% w/v of the compound of Formula 1;
about 0.3% w/v thiosulfate salt;
sodium chloride; and
sodium phosphate,
wherein the composition has a pH of about 7.0 to about 8.0.
12. The composition of claim 11 , wherein the sodium phosphate is dibasic sodium phosphate.
13. A composition comprising:
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.
14. A composition comprising:
about 5 w/v % compound of Formula 1:
or a salt thereof;
about 0.3% w/v antioxidant, the antioxidant being 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;
wherein the composition is an aqueous solution having the compound of Formula 1 dissolved therein, and
wherein the composition is suitable for topical administration to the eye.
15. The composition of claim 13 , wherein said thiosulfate salt is the primary antioxidant.
16. The composition of claim 13 , further comprising a sparged inert gas.
17. The composition of claim 16 , wherein the sparged inert gas is nitrogen.
18. The composition of claim 13 , wherein the composition is buffered to a pH of about 7.5.
19. The composition of claim 1 , wherein the composition comprises one or more antioxidants and a sparged inert gas.
20. The composition of claim 1 , wherein the formulation expires in about 1-5 years when stored at or below ambient temperature.
21. The composition of claim 14 , wherein the formulation expires in about 1-5 years when stored at or below ambient temperature.