Atropine pharmaceutical compositions
View Patent ↗The inventive subject matter is directed to compositions and methods for sterile and storage stable low-dose atropine formulations with improved stability. Most preferably, the compositions presented herein are substantially preservative free and exhibit less than 0.35% tropic acid from degradation of atropine. Advantageously, contemplated formulations are also substantially free of preservatives.
1. A treatment kit for treatment of myopia, comprising:
a first container that contains a liquid storage-stable low-dose atropine ophthalmic formulation, wherein the first container is configured as a disposable single-use container or a multi-dose container; and
a second container enclosing the first container;
wherein the liquid storage-stable low-dose atropine ophthalmic formulation comprises an aqueous solution comprising a buffer, a tonicity agent, a viscosity modifier, and atropine or a pharmaceutically acceptable salt thereof;
wherein the atropine or the pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of equal or less than 0.05 wt %;
wherein the buffer has a concentration of equal or less than 75 mM, and wherein the ophthalmic atropine composition has a pH of between 5.0 and 6.0; and
wherein the ophthalmic atropine composition after storage over at least two months at 25° C. and 60% relative humidity contains equal or less than 0.35% tropic acid formed from degradation of the atropine.
2. The kit of claim 1 , wherein the first container is a blow-fill-seal (BSF) container or wherein the second container is a laminated metallized pouch.
3. The kit of claim 1 , wherein the atropine or a pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of between 0.01 wt % and 0.05 wt %.
4. The kit of claim 1 , wherein the buffer comprises monobasic and dibasic sodium phosphate.
5. The kit of claim 1 , wherein the buffer has a concentration of equal or less than 75 mM.
6. The kit of claim 1 , wherein the buffer has a concentration of equal or less than 50 mM.
7. The kit of claim 1 , wherein the treatment of myopia is treatment of pediatric myopia.
8. The kit of claim 1 , further comprising a chelator selected from the group consisting of a bicarboxylic acid, a tricarboxylic acid, and an aminopolycarboxylic acid.
9. The kit of claim 8 , wherein the chelator is present in the ophthalmic atropine composition in an amount of equal or less than 0.01 wt %.
10. The kit of claim 1 , wherein the ophthalmic atropine composition has a pH of 5.5 (+/−0.2).
11. The kit of claim 1 , wherein the tonicity agent is a pharmaceutically acceptable salt and wherein the salt is present in the ophthalmic atropine composition in an amount of between 0.2 wt % and 0.8 wt %.
12. The kit of claim 1 , wherein the viscosity modifier is a modified cellulose selected from the group consisting of a hydroxyethyl cellulose, a hydroxypropyl cellulose, or a hydroxypropyl methylcellulose.
13. The kit of claim 1 , wherein the ophthalmic atropine composition is substantially free of a preservative.
14. A method of treating myopia, comprising:
administering to an eye a liquid storage-stable low-dose atropine ophthalmic formulation that comprises an aqueous solution comprising a buffer, a tonicity agent, a viscosity modifier, and atropine or a pharmaceutically acceptable salt thereof;
wherein the atropine or the pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of equal or less than 0.05 wt %;
wherein the buffer has a concentration of equal or less than 75 mM, and wherein the ophthalmic atropine composition has a pH of between 5.0 and 6.0; and
wherein the ophthalmic atropine composition after storage over at least two months at 25° C. and 60% relative humidity contains equal or less than 0.35% tropic acid formed from degradation of the atropine.
15. The method of claim 14 , wherein the myopia is a pediatric myopia.
16. The method of claim 14 , wherein the atropine or a pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of between 0.01 wt % and 0.02 wt %.
17. The method of claim 14 , wherein the buffer has a concentration of equal or less than 50 mM.
18. The method of claim 14 , wherein the low-dose atropine ophthalmic formulation further comprises a chelator selected from the group consisting of a bicarboxylic acid, a tricarboxylic acid, and an aminopolycarboxylic acid, and wherein the chelator is present in the ophthalmic atropine composition in an amount of equal or less than 0.01 wt %.
19. The method of claim 14 , wherein the low-dose atropine ophthalmic formulation has a pH of 5.5 (+/−0.2).
20. The method of claim 14 , wherein the low-dose atropine ophthalmic formulation is substantially free of a preservative.