COMPOSITIONS AND METHODS FOR THE TREATMENT OF PRESBYOPIA
The invention provides compositions and methods for the treatment of presbyopia. The compositions preferably comprise aceclidine and a cryoprotectant. The compositions optionally contain a cycloplegic agent, a surfactant, a viscosity enhancer, an osmolarity modifier and a preservative.
1 . A method of stabilizing a composition comprising aceclidine comprising storing the composition in a container having a headspace at a temperature from about 2 degrees Celsius to about 8 degrees Celsius.
2 . The method of claim 1 , wherein the composition is filled into the container under a nitrogen overlay.
3 . The method of claim 2 , wherein the headspace is purged with nitrogen.
4 . The method of claim 1 , wherein aceclidine is at a concentration from about 0.25% to about 4.0% w/v aceclidine, wherein w/v denotes weight by total volume of the composition.
5 . The method of claim 1 , wherein the method provides at least 90% stability of aceclidine for at least 7 months.
6 . The method of claim 3 , wherein the method provides at least 90% stability of aceclidine for at least 12 months.
7 . The method of claim 1 , wherein the composition further comprises a viscosity enhancer, a polysorbate, a cryoprotectant and a preservative.
8 . The method of claim 7 , wherein the method provides at least 90% stability of aceclidine for at least 18 months.
9 . The method of claim 7 , wherein the viscosity enhancer provides a viscosity of at least 50 centipoise.
10 . The method of claim 7 , wherein the cryoprotectant is selected from the group consisting of a polyol, a sugar, an alcohol, a lower alkanol, a lipophilic solvent, a hydrophilic solvent, a bulking agent, a solubilizer, a surfactant, an antioxidant, a cyclodextrin, a maltodextrin, colloidal silicon dioxide, polyvinyl alcohol, 2-methyl-2,4-pentanediol, cellobiose, gelatin, polyethylene glycol (PEG), dimethyl sulfoxide (DMSO), formamide, antifreeze protein 752 or a combination thereof.
11 . The method of claim 7 , wherein the preservative is selected from the group consisting of benzalkonium chloride, sorbate, an antioxidant and a combination thereof.
12 . The method of claim 9 , wherein the antioxidant is selected from the group consisting of sodium ascorbate, sodium bisulfate, sodium metabisulfite, n-acetyl cysteine and a combination thereof.
13 . A method of stabilizing a composition comprising aceclidine, hydroxypropylmethyl cellulose, polysorbate 80, mannitol, sorbate and an antioxidant selected from the group consisting of sodium ascorbate, sodium bisulfate, sodium metabisulfite, n-acetyl cysteine or a combination thereof comprising storing the composition in a container having a headspace at a temperature from about 2 degrees Celsius to about 8 degrees Celsius, wherein the composition is filled into the container under a nitrogen overlay and the headspace is purged with nitrogen.
14 . The method of claim 13 , wherein the aceclidine is at a concentration from about 0.25% to about 4.00% w/v, the hydroxypropylmethyl cellulose is at a concentration from about 0.75% to about 1.25% w/v, polysorbate 80 is at a concentration from about 2% to about 4% w/v, mannitol is at a concentration from about 2% to about 4% w/v, sorbate is at a concentration from about 0.10% to about 0.12% w/v and the antioxidant is at a concentration from about 0.10% to about 0.25% w/v, wherein w/v denotes weight by total volume of the composition.
15 . The method of claim 14 , wherein the method provides at least 90% stability of aceclidine for at least 20 months.
16 . The method of claim 15 , wherein the method provides at least 90% stability of aceclidine for at least 22 months.
17 . A container comprising aceclidine prepared by the process comprising the steps of:
a) providing a container;
b) filling the container with a composition comprising aceclidine under a nitrogen overlay;
c) purging a headspace created during the filling step b) with nitrogen;
d) capping the container.
18 . The container of claim 17 , wherein the process further comprises the step of storing the container at a temperature from about 2 to about 8 degrees Celsius.
19 . The container of claim 17 , wherein the composition further comprises a preservative selected from the group consisting of sorbate, benzalkonim chloride, sodium ascorbate, sodium bisulfate, sodium metabisulfite, n-acetyl cysteine and a combination thereof.
20 . The container of claim 17 , wherein the composition has a viscosity of at least 50 centipoise.
21 . A composition comprising from about 0.25% to about 4.0% w/v aceclidine and one or more means of stabilizing the composition selected from the group consisting of filling the composition into a container under a nitrogen overlay and purging a headspace created during filling with nitrogen, having a total viscosity of the composition of at least 50 centipoise or more, adding a preservative to the composition selected from the group consisting of sorbate, benzalkonim chloride, sodium ascorbate, sodium bisulfate, sodium metabisulfite, n-acetyl cysteine and a combination thereof,
wherein the composition is stored at a temperature from about 2 to about 8 degrees Celsius and wherein w/v denotes weight by total volume of the composition.