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. A method for treating presbyopia in a subject in need thereof, the method comprising:
(a) providing an aqueous ophthalmological solution comprising aceclidine, wherein the aqueous ophthalmological solution does not comprise a cycloplegic agent;
(b) storing the aqueous ophthalmological solution in a container having a headspace at a temperature from about 2 degrees Celsius to about 8 degrees Celsius for at least 7 months to provide a stored aqueous ophthalmological solution; and
(c) administering the stored aqueous ophthalmological solution to the subject in need thereof, wherein upon administration, the stored aqueous ophthalmological solution comprises at least 90% of the aceclidine that the aqueous ophthalmological solution comprised at the onset of the storing;
thereby treating the presbyopia in the subject.
2. The method of claim 1 , wherein the aqueous ophthalmological solution is stored for at least 12 months.
3. The method of claim 2 , wherein the aqueous ophthalmological solution is stored for at least 18 months.
4. The method of claim 3 , wherein the aqueous ophthalmological solution is stored for at least 24 months.
5. The method of claim 1 , wherein the aqueous ophthalmological solution has a viscosity of about 1 centipoise (cp) to about 25 cps at a high shear of blinking and a viscosity of about 50 cps to about 200 cps at a low shear between blinks.
6. The method of claim 1 , wherein the aqueous ophthalmological solution comprises a pH from about 4.0 to about 8.0.
7. The method of claim 1 , wherein the 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 aqueous ophthalmological solution.
8. The method of claim 7 , wherein the aceclidine is at a concentration from about 0.50% to about 1.90% w/v aceclidine, wherein w/v denotes weight by total volume of the aqueous ophthalmological solution.
9. The method of claim 8 , wherein the aceclidine is at a concentration from about 1.65% to about 1.85% w/v aceclidine, wherein w/v denotes weight by total volume of the aqueous ophthalmological solution.
10. The method of claim 1 , wherein the aqueous ophthalmological solution further comprises a surfactant.
11. The method of claim 1 , wherein the aqueous ophthalmological solution further comprises a viscosity enhancer.
12. The method of claim 11 , wherein the aceclidine remains in the aqueous ophthalmological solution for at least 7 additional months in comparison to an aqueous ophthalmological solution not comprising the viscosity enhancer.
13. The method of claim 1 , wherein the aqueous ophthalmological solution is stored for 7 months to 18 months.
14. The method of claim 1 , wherein the aqueous ophthalmological solution is stored for 7 months.
15. The method of claim 1 , wherein the aqueous ophthalmological solution is stored for about 12 months.
16. The method of claim 1 , wherein the aqueous ophthalmological solution is stored for about 15 months.
17. The method of claim 1 wherein the aqueous ophthalmological solution further comprises a cryoprotectant.
18. The method of claim 1 , wherein the aqueous ophthalmological solution further comprises a polyol.
19. The method of claim 1 , wherein the aqueous ophthalmological solution further comprises mannitol.
20. The method of claim 1 , wherein a cycloplegic agent is not administered to the subject.