Carboxylvinyl polymer-containing nanoparticle suspensions
View Patent ↗The present invention generally relates to suspension compositions having a carboxyvinyl polymer such as a carbomer, a galactomannan such as guar, and a borate compound. A sparingly soluble particulate compound such as nepafenac is also included in the compositions. The sparingly soluble particulate compound has a small particle size to enhance bioavailability of the compound.
1. A topically administrable aqueous ophthalmic suspension composition comprising:
a carboxyvinyl polymer at a concentration of 0.1 to 0.5 w/v %, and wherein said carboxyvinyl polymer is a carbomer;
a galactomannan at a concentration of 0.1 to 0.4 w/v %, said galactomannan selected from the group consisting of guar, native guar, and hydroxypropyl guar;
borate at a concentration of 0.4 to 2.0 w/v %; and
a sparingly soluble particulate compound, said compound having a solubility in water at 25° C. of 0.001 to 0.1 w/v % and wherein said sparingly soluble particulate compound is nepafenac at a concentration of 0.1 to 1.0 w/v %.
2. A composition according to claim 1 , further comprising a pH-adjusting agent in an amount sufficient to cause the composition to have a pH of 5.0 to 7.2.
3. A composition according to claim 1 , further comprising a tonicity-adjusting agent in an amount sufficient to cause the composition to have an osmolality of 250 to 350 mOsm/kg.
4. A composition according to claim 1 wherein said carboxyvinyl polymer is carbomer at a concentration of 0.4 w/v %.
5. A composition according to claim 1 further comprising a milling agent at a concentration of 0.005 to 0.1 w/v %.
6. A composition according to claim 5 wherein said milling agent is a surfactant or polymer.
7. A composition according to claim 6 wherein said milling agent is sodium carboxylmethylcellulose.
8. A composition according to claim 1 further comprising a metal chloride salt tonicity-adjusting agent.
9. A composition according to claim 8 wherein said metal chloride salt is sodium chloride at a concentration of 0.4 w/v %.
10. A composition according to claim 1 further comprising a non-ionic hydroxyl compound as a tonicity-adjusting agent.
11. A composition according to claim 1 further comprising both a preservative and a chelating agent.
12. A composition according to claim 11 wherein the preservative is benzalkonium chloride at a concentration of 0.005 w/v % and the chelating agent is edetate disodium at a concentration of 0.01 w/v %.
13. A composition according to claim 1 wherein said carboxyvinyl polymer is carbomer, said galactomannan is native guar, said borate is boric acid, and said sparingly soluble particulate compound is nepafenac at a concentration of 0.1 to 1.0 w/v %.
14. A composition according to claim 13 comprising 0.4 w/v % carbomer, 0.2 w/v % native guar, 0.5 w/v % boric acid, and 0.3 w/v % nepafenac.
15. A composition according to claim 14 wherein said nepafenac has an average particle size of 400 nm.
16. The composition according to claim 2 , further comprising a pH adjusting agent in an amount sufficient to cause the composition to have a pH of 7.0.
17. The composition according to claim 7 wherein said milling agent is 0.06 w/v % sodium carboxymethylcellulose.
18. The composition according to claim 10 , wherein said non-ionic hydroxyl compound is propylene glycol at a concentration of 0.5 w/v %.
19. The composition according to claim 1 wherein said carboxylvinyl polymer is Carbopol® 974p.
20. The composition according to claim 19 wherein said carboxylvinyl polymer is present at a concentration of 0.4 w/v %.
21. The composition according to claim 1 wherein said galactomannan is guar or native guar.
22. The composition according to claim 21 wherein said galactomannan is present at a concentration of 0.2 w/v %.
23. The composition according to claim 1 wherein said borate is boric acid.
24. The composition according to claim 23 wherein said borate is present at a concentration of 0.4 to 0.6 w/v %.
25. The composition according to claim 24 wherein said borate is present at a concentration of 0.5 w/v %.
26. The composition according to claim 1 wherein said sparingly soluble particulate compound is present at a concentration of 0.25 to 0.35 w/v %.
27. The composition according to claim 1 wherein said sparingly soluble particulate compound is present at a concentration of 0.3 w/v %.
28. The composition according to claim 1 further comprising a chelating agent.
29. The composition according to claim 28 wherein said chelating agent is edetate disodium.
30. The composition according to claim 29 wherein said chelating agent is present at a concentration of 0.001 to 0.1 w/v %.
31. The composition according to claim 30 wherein said chelating agent is present at a concentration of 0.01 w/v %.
32. A topically administrable ophthalmic suspension composition consisting essentially of
a) 0.3 w/v % nepafenac;
b) 0.4 w/v % carbomer;
c) 0.2 w/v % native guar;
d) 0.5 w/v % boric acid;
e) 0.06 w/v % sodium carboxymethylcellulose;
f) 0.4 w/v % sodium chloride;
g) 0.5 w/v % propylene glycol;
i) 0.005% (w/v) benzalkonium chloride;
j) 0.01% edetate disodium; and
k) purified water.