Stable ophthalmic formulations of a fluorinated integrin antagonist
AssigneeOcuTerra Therapeutics, Inc.
InventorsD. Scott Edwards, Ben C. Askew
Life of this patent
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Abstract
The invention provides stable ophthalmic formulations, a unit dose containing such formulations, medical kits, and methods for making and using such formulations and unit doses to treat patients suffering from a disorder mediated by an αv integrin, such as diabetic retinopathy.
Claims127
An aqueous, ophthalmic solution, comprising:
- a. from 4.7% (w/v) to 5.3% (w/v) of a compound of Formula I:
- b. from 14% (w/v) to 18% (w/v) of a cyclodextrin;
- c. from 0.1% (w/v) to 5% (w/v) of a buffer;
- d. from 0.01% (w/v) to 1% (w/v) of a preservative;
- and
- e. at least 75% (w/v) water;
- wherein the solution has a pH in the range of 7.5 to 8.7.
An aqueous, ophthalmic solution, comprising:
- a. from 4.9% (w/v) to 5.1% (w/v) of a compound of Formula I:
- b. from 15% (w/v) to 16% (w/v) of 2-hydroxypropyl-β-cyclodextrin;
- c. from 0.5% (w/v) to 1.5% (w/v) of a buffer comprising boric acid;
- d. from 0.01% (w/v) to 0.2% (w/v) of a benzalkonium salt;
- and
- e. at least 75% (w/v) water;
- wherein the solution has a pH in the range of 7.8 to 8.5.
An aqueous, ophthalmic solution, comprising:
- a. 5.5% (w/v) of a compound of Formula I:
- b. about 15.5% (w/v) of 2-hydroxypropyl-β-cyclodextrin;
- c. about 1% (w/v) of a buffer comprising boric acid;
- d. about 0.02% (w/v) of a benzalkonium salt;
- and
- e. at least 75% (w/v) water;
- wherein the solution has a pH in the range of 7.8 to 8.5.
An aqueous, ophthalmic solution, comprising:
- a. 5.5% (w/v) of a compound of Formula I:
- b. 15.5% (w/v) of 2-hydroxypropyl-β-cyclodextrin;
- c. 1% (w/v) of a buffer comprising boric acid;
- d. 0.02% (w/v) of a benzalkonium salt;
- and
- e. at least 75% (w/v) water;
- wherein the solution has a pH in the range of 7.8 to 8.5.
The solution of any one of claims 1-65, wherein the solution contains less than 1% (w/w) of a precipitate that is (S)-3-(6-(difluoromethoxy)pyridin-3-yl)-3-(2-oxo-3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)imidazolidin-1-yl)propanoic acid hydrate.
An aqueous, ophthalmic solution, consisting of:
- a. from 4.9% (w/v) to 5.1% (w/v) of a compound of Formula I:
- b. from 15% (w/v) to 16% (w/v) of 2-hydroxypropyl-β-cyclodextrin;
- c. from 0.5% (w/v) to 1.5% (w/v) of a buffer comprising boric acid;
- d. from 0.01% (w/v) to 0.5% (w/v) of a benzalkonium salt;
- e. at least 75% (w/v) water;
- and
- f. one or more excipients independently selected from the group consisting of a pH adjuster and a tonicity modifier;
- wherein the solution has a pH in the range of 7.8 to 8.5.
An aqueous, ophthalmic solution, consisting of:
- a. 5.5% (w/v) of a compound of Formula I:
- b. about 15.5% (w/v) of 2-hydroxypropyl-β-cyclodextrin;
- c. about 1% (w/v) of a buffer comprising boric acid;
- d. about 0.02% (w/v) of a benzalkonium salt;
- and
- e. at least 75% (w/v) water;
- and
- f. one or more excipients independently selected from the group consisting of a pH adjuster and a tonicity modifier;
- wherein the solution has a pH in the range of 7.8 to 8.5.
An aqueous, ophthalmic solution, consisting of:
- a. 5.5% (w/v) of a compound of Formula I:
- b. 15.5% (w/v) of 2-hydroxypropyl-β-cyclodextrin;
- c. 1% (w/v) of a buffer comprising boric acid;
- d. 0.02% (w/v) of a benzalkonium salt;
- and
- e. at least 75% (w/v) water;
- and
- f. one or more excipients independently selected from the group consisting of a pH adjuster and a tonicity modifier;
- wherein the solution has a pH in the range of 7.8 to 8.5.
An aqueous, ophthalmic solution, comprising:
- a. from about 4% (w/v) to about 6% (w/v) of a compound of Formula II or a pharmaceutically acceptable salt thereof:
- b. from 14% (w/v) to 18% (w/v) of a cyclodextrin;
- c. a buffer;
- d. a preservative;
- and
- e. at least 75% (w/v) water;
- wherein the solution has a pH in the range of 7.5 to 8.7.
The compound (S)-3-(6-(difluoromethoxy)pyridin-3-yl)-3-(2-oxo-3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)imidazolidin-1-yl)propanoic acid hydrate.
A method of preparing an aqueous, ophthalmic solution, the method comprising:
- a. providing a first mixture comprising water, a cyclodextrin, and a compound of Formula I:
- b. admixing a preservative and the first mixture, to thereby provide the aqueous, ophthalmic solution.
Dependencies are inferred from the claim text.