COMPOSITIONS AND METHODS FOR STORAGE STABLE OPHTHALMIC DRUGS
The present invention is related to methods of stabilizing an ophthalmic drug by adding a surfactant and a viscosity enhancer to the ophthalmic drug to create a composition wherein the composition has a viscosity of about 25 centipoise or less at a shear rate of 1/1000 per second at 25 degrees Celsius and a viscosity of about 70 centipoise or more at shear rate of 1 per second at 25 degrees Celsius, filling the composition into a container; and storing the container at a temperature from about 2 degrees Celsius to about 25 degrees Celsius. The present invention is further directed to a container prepared by the methods of the present invention.
1 .- 22 . (canceled)
23 . A method of treating presbyopia in a human, comprising:
(a) storing an aqueous ophthalmological composition comprising aceclidine at a concentration from about 0.25% to about 4.0% w/v, mannitol at a concentration from about 2.0% to about 4.0% w/v, and water, in a vial at a temperature from about 2 degrees Celsius to about 8 degrees Celsius, wherein w/v denotes weight by total volume of the aqueous ophthalmological composition, and wherein the vial comprises a cap and a headspace between the aqueous ophthalmological composition and the cap, wherein the cap prevents the aqueous ophthalmological composition from exiting the vial when stored; and
(b) administering two drops of the stored aqueous ophthalmological composition from the vial to each eye of the human with presbyopia, wherein administration of two drops to each eye provides near vision improvement for about 10 hours;
wherein the aqueous ophthalmological composition lacks a cycloplegic;
wherein when the vial is stored at the temperature from about 2 degrees Celsius to about 8 degrees Celsius for at least 7 months, the stored aqueous ophthalmological composition comprises at least 90% of the aceclidine that the composition comprised at the onset of storing.
24 . The method of claim 23 , wherein when the vial is stored at the temperature from about 2 degrees Celsius to about 8 degrees Celsius for at least 12 months, the stored aqueous ophthalmological composition comprises at least 90% of the aceclidine that the aqueous ophthalmological composition comprised at the onset of storing.
25 . The method of claim 23 , wherein when the vial is stored at the temperature from about 2 degrees Celsius to about 8 degrees Celsius for at least 18 months, the stored aqueous ophthalmological composition comprises at least 90% of the aceclidine that the aqueous ophthalmological composition comprised at the onset of storing.
26 . The method of claim 23 , wherein when the vial is stored at the temperature from about 2 degrees Celsius to about 8 degrees Celsius for at least 24 months, the stored aqueous ophthalmological composition comprises at least 90% of the aceclidine that the aqueous ophthalmological composition comprised at the onset of storing.
27 . The method of claim 23 , wherein the aqueous ophthalmological composition has a viscosity of about 1 centipoise (cp) to about 25 cps at a high shear rate of blinking and a viscosity of about 50 cps to about 200 cps at a low shear rate between blinks.
28 . The method of claim 23 , wherein the aqueous ophthalmological composition has a pH from about 4.0 to about 8.0.
29 . The method of claim 28 , wherein the pH is from about 5.0 to about 7.0.
30 . The method of claim 23 , wherein the aceclidine is at a concentration from about 0.25% to about 2.0% w/v.
31 . The method of claim 30 , wherein the aceclidine is at a concentration from about 0.5% to about 1.9% w/v.
32 . The method of claim 23 , wherein the aqueous ophthalmological composition further comprises a surfactant.
33 . The method of claim 32 , wherein the surfactant comprises polysorbate 80.
34 . The method of claim 33 , wherein the polysorbate 80 is at a concentration from about 1.0% to about 5.0% w/v.
35 . The method of claim 23 , wherein the aqueous ophthalmological composition further comprises a viscosity agent.
36 . The method of claim 35 , wherein the viscosity agent comprises hydroxypropyl methylcellulose (HPMC).
37 . The method of claim 36 , wherein the HPMC is at a concentration from about 0.25% to about 2.0% w/v.
38 . A method of treating presbyopia in a human, comprising:
(a) storing an aqueous ophthalmological composition comprising aceclidine, mannitol, hydroxypropyl methylcellulose (HPMC) and polysorbate 80 in a vial at a temperature from about 2 degrees Celsius to about 8 degrees Celsius, wherein the vial comprises a cap and a headspace between the aqueous ophthalmological composition and the cap, wherein the cap prevents the aqueous ophthalmological composition from exiting the vial when stored; and
(b) administering two drops of the stored aqueous ophthalmological composition to each eye of the human with presbyopia, wherein administration of two drops to each eye produces near vision improvement for about 10 hours;
wherein the aqueous ophthalmological composition lacks a cycloplegic,
wherein when the vial is stored at the temperature from about 2 degrees Celsius to about 8 degrees Celsius for at least 7 months, the stored aqueous ophthalmological composition comprises at least 90% of the aceclidine that the composition comprised at the onset of storing.
39 . The method of claim 38 , wherein the HPMC is at a concentration from about 0.25% to about 2.0% w/v, wherein w/v denotes weight by total volume of the aqueous ophthalmological composition.
40 . The method of claim 38 , wherein the polysorbate 80 is at a concentration from about 1.0% to about 5.0% w/v, wherein w/v denotes weight by total volume of the aqueous ophthalmological composition.
41 . A method of treating presbyopia in a human, comprising:
(a) storing an aqueous ophthalmological composition comprising aceclidine at a concentration from about 0.25% to about 4.0% w/v, mannitol, hydroxypropyl methylcellulose (HPMC), water, polysorbate 80, and water in a vial at a temperature from about 2 degrees Celsius to about 8 degrees Celsius, wherein w/v denotes weight by total volume of the aqueous ophthalmological composition, and wherein the vial comprises a cap and a headspace between the aqueous ophthalmological composition and the cap,