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 liquid storage-stable low-dose ophthalmic atropine composition, consisting essentially of:
an aqueous solution comprising a buffer, a tonicity agent, a chelator, 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 composition of claim 1 , wherein the atropine or the pharmaceutically acceptable salt thereof is atropine sulfate.
3. The composition of claim 1 , wherein the atropine or a pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of equal or less than 0.02 wt %.
4. The composition of claim 1 , wherein the atropine or a pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of equal or less than 0.01 wt %.
5. The composition of claim 1 , wherein the atropine or a pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of between 0.001 wt % and 0.01 wt %.
6. The composition of claim 2 , wherein the buffer has a concentration of equal or less than 60 mM.
7. The composition of claim 5 , wherein the buffer has a concentration of equal or less than 50 mM.
8. The composition of claim 6 , wherein the buffer comprises monobasic and dibasic sodium phosphate.
9. The composition of claim 7 , wherein the buffer comprises monobasic and dibasic sodium phosphate.
10. The composition of claim 1 , wherein the chelator is selected from the group consisting of a bicarboxylic acid, a tricarboxylic acid, and an aminopolycarboxylic acid.
11. The composition of claim 8 , wherein the chelator is ethylenediaminetetraacetic acid (EDTA).
12. The composition of claim 9 , wherein the chelator is ethylenediaminetetraacetic acid (EDTA).
13. The composition of claim 10 wherein the chelator is present in the ophthalmic atropine composition in an amount of equal or less than 0.01 wt %.
14. The composition of claim 1 , wherein the ophthalmic atropine composition has a pH of between 5.0 (+/−0.2) and 5.5 (+/−0.2).
15. The composition of claim 1 , wherein the ophthalmic atropine composition has a pH of between 5.5 (+/−0.2) and 6.0 (+/−0.2).
16. The composition 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 %.
17. The composition of claim 1 , wherein the viscosity modifier is a hydroxyethyl cellulose, a hydroxypropyl cellulose, or a hydroxypropyl methylcellulose.
18. The composition of claim 1 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.
19. The composition of claim 1 , wherein the atropine or a pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of between 0.001 wt % and 0.01 wt %, wherein the buffer comprises monobasic and dibasic sodium phosphate and has a concentration of equal or less than 50 mM, wherein the viscosity modifier is a hydroxyethyl cellulose, a hydroxypropyl cellulose, or a hydroxypropyl methylcellulose, and wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.
20. The composition 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 %, wherein the buffer comprises monobasic and dibasic sodium phosphate and has a concentration of equal or less than 50 mM, wherein the viscosity modifier is a hydroxyethyl cellulose, a hydroxypropyl cellulose, or a hydroxypropyl methylcellulose, and wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.