Carboxyvinyl 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:
carbomer at a concentration of 0.1 to 0.5 w/v %;
guar at a concentration of 0.1 to 0.4 w/v %;
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 a particle size of 50 to 700 nm, and wherein said sparingly soluble particular compound is nepafenac at a concentration of 0.25 to 0.35 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 carbomer is 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 comprising 0.4 w/v % carbomer, 0.2 w/v % guar, 0.5 w/v % boric acid, and 0.3 w/v % nepafenac.
14. A composition according to claim 13 wherein said nepafenac has an average particle size of 400 nm.
15. A topically administrable ophthalmic suspension composition consisting essentially of
a) 0.3 w/v % nepafenac having a particle size of 50 to 700 nm;
b) 0.4 w/v % carbomer;
c) 0.2 w/v % 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;
h) a pH-adjusting agent in an amount sufficient to cause the composition to have a pH of 7.0;
i) 0.005% (w/v) benzalkonium chloride;
j) 0.01% edetate disodium; and
k) purified water.