OPHTHALMIC PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
Provided herein are ophthalmic pharmaceutical compositions comprising (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide (WS-12) for effectively treating dry eye in a subject in need thereof, effectively reducing dry eye in a subject in need thereof, effectively reducing the likelihood of dry eye in a subject in need thereof, or for treating, preventing, or ameliorating signs or symptoms of dry eye in a subject in need thereof.
1 . A liquid ophthalmic pharmaceutical composition, comprising:
a viscosity of less than 5 cP;
0.0005% w/v to 0.01% w/v (1 R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide or a pharmaceutically acceptable salt thereof;
0.1% w/v to 5 w/v of a solubilizing agent;
0.1% w/v to 0.5% w/v of a viscosity modifier;
a buffer; and
0.1% w/v to 1.0% w/v of a tonicity agent.
2 . The liquid ophthalmic pharmaceutical composition of claim 1 , having a pH of 5.0 to 8.5.
3 . The liquid ophthalmic pharmaceutical composition of claim 1 , having a pH of 6.7 to 7.3.
4 . (canceled)
5 . The liquid ophthalmic pharmaceutical composition of claim 3 , wherein the pH is about 7.
6 . The liquid ophthalmic pharmaceutical composition of claim 1 , wherein the solubilizing agent is selected from polyethylene glycol 400, castor oil, polyoxyethylene (20) sorbitan mono-oleate, or polyoxyl 35 castor oil.
7 . The liquid ophthalmic pharmaceutical composition of claim 1 , wherein the solubilizing agent is polyoxyl 35 castor oil.
8 . The liquid ophthalmic pharmaceutical composition of claim 1 , wherein the viscosity modifier is selected from a cellulose derivative, a clay a natural gum, a synthetic polymer, colloidal silicon dioxide, or any combination thereof.
9 . The liquid ophthalmic pharmaceutical composition of claim 8 , wherein:
the cellulose derivative is selected from methylcellulose, microcrystalline cellulose, carboxymethylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, or hydroxypropyl methylcellulose;
the clay is selected from hectorite, bentonite, aluminum silicate, magnesium silicate, kaolin, or a combination thereof; and
the natural gum is selected from acacia, guar gum, tragacanth, xanthan gum, alginate, carrageenan, or locust bean gum.
10 . The liquid ophthalmic pharmaceutical composition of claim 1 , wherein the viscosity modifier comprises hydroxypropyl methylcellulose.
11 . The liquid ophthalmic pharmaceutical composition of claim 1 , wherein the tonicity agent is selected from dextrose, glycerin, mannitol, potassium chloride, or sodium chloride.
12 . The liquid ophthalmic pharmaceutical composition of claim 1 , wherein the tonicity agent is sodium chloride.
13 . The liquid ophthalmic pharmaceutical composition of claim 1 , wherein the buffer is selected from a phosphate buffer, a citrate buffer, TRIS Base, TRIS HCl, PBS, HEPES, MES, PIPES, or TES.
14 . The liquid ophthalmic pharmaceutical composition of claim 1 , wherein the buffer is a phosphate buffer.
15 - 32 . (canceled)
33 . The liquid ophthalmic pharmaceutical composition of claim 1 , comprising:
a viscosity of less than 5 cP;
about 0.003% w/v (1 R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide;
about 0.14% w/v hypromellose;
about 3.0% w/v polyoxyl 35 castor oil;
about 0.78% w/v a phosphate buffer;
about 0.55% w/v NaCl;
a pH of about 7; and
water.
34 . The liquid ophthalmic pharmaceutical composition of claim 1 , comprising:
a viscosity of less than 5 cP;
0.003±15% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide;
0.14±15% w/v hypromellose;
3.0±15% w/v polyoxyl 35 castor oil;
0.78±15% w/v a phosphate buffer;
0.55±15% w/v NaCl;
a pH of about 7; and
water.
35 . The liquid ophthalmic pharmaceutical composition of claim 1 , comprising:
a viscosity of less than 5 cP;
0.003±10% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide;
0.14±10% w/v hypromellose;
3.0±10% w/v polyoxyl 35 castor oil;
0.78±10% w/v a phosphate buffer;
0.55±10% w/v NaCl;
a pH of about 7; and
water.
36 . The liquid ophthalmic pharmaceutical composition of claim 1 , comprising:
a viscosity of less than 5 cP;
about 0.0014% w/v (1 R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide;
about 0.14% w/v hypromellose;
about 3.0% w/v polyoxyl 35 castor oil;
about 0.78% w/v a phosphate buffer;
about 0.55% w/v NaCl;
a pH of about 7; and
water.
37 . The liquid ophthalmic pharmaceutical composition of claim 1 , comprising:
a viscosity of less than 5 cP;
0.0014±15% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide;
0.14±15% w/v hypromellose;
3.0±15% w/v polyoxyl 35 castor oil;
0.78±15% w/v a phosphate buffer;
0.55±15% w/v NaCl;
a pH of about 7; and
water.
38 . The liquid ophthalmic pharmaceutical composition of claim 1 , comprising:
a viscosity of less than 5 cP;
0.0014±10% w/v (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide;
0.14±10% w/v hypromellose;
3.0±10% w/v polyoxyl 35 castor oil;
0.78±10% w/v a phosphate buffer;
0.55±10% w/v NaCl;
a pH of about 7; and
water.