Atropine pharmaceutical compositions
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 storage-stable preservative-free ophthalmic atropine composition, comprising:
an aqueous solution comprising low-dose atropine or a pharmaceutically acceptable salt thereof, a tonicity agent, and a cellulosic viscosity modifier; wherein the aqueous solution contains no buffer,
wherein the low-dose atropine or pharmaceutically acceptable salt thereof is present at a concentration of equal or less than 0.05 wt %;
wherein the ophthalmic atropine composition contains not more than 0.01 wt % of a preservative;
wherein the pH of the ophthalmic formulation is between 5.0 and 6.0; and
wherein the ophthalmic formulation after storage for 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 ophthalmic formulation after storage for two months at 25° C. and 60% relative humidity contains equal or less than 0.30% tropic acid formed from degradation of the atropine.
3. The composition of claim 1 , wherein the ophthalmic formulation after storage for two months at 40° C. and 75% relative humidity contains equal or less than 1.50% tropic acid formed from degradation of the atropine.
4. The composition of claim 1 , wherein the low-dose atropine or pharmaceutically acceptable salt thereof is present at a concentration of equal or less than 0.01 wt %.
5. The composition of claim 1 , wherein the low-dose atropine or pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of between 0.01% and 0.05 wt %.
6. The composition of claim 1 , wherein the low-dose atropine or pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of between 0.001 wt % and 0.01 wt %.
7. The composition of claim 1 , wherein the low-dose atropine or pharmaceutically acceptable salt thereof is atropine sulfate.
8. The composition of claim 1 , wherein the ophthalmic atropine composition has a pH of between 5.3 and 5.8.
9. The composition of claim 1 , further comprising a chelator.
10. The composition of claim 9 , wherein the chelator is present in an amount of 0.01 wt % or less.
11. The composition of claim 9 , wherein the chelator is selected from the group consisting of a bicarboxylic acid, a tricarboxylic acid, and an aminopolycarboxylic acid.
12. The composition of claim 1 , wherein the tonicity agent is present in the ophthalmic atropine composition in an amount to adjust osmolality of the composition to 260-340 mOsm/kg.
13. The composition of claim 1 , wherein the tonicity agent is sodium chloride and wherein sodium chloride is present in the ophthalmic atropine composition in an amount ranging from 0.3 wt % to 0.7 wt %.
14. The composition of claim 1 , wherein the cellulosic viscosity modifier is a hydroxyethyl cellulose, a hydroxypropyl cellulose, or a hydroxypropyl methylcellulose.
15. The composition of claim 1 , wherein the cellulosic viscosity modifier is present in an amount ranging from 0.4 wt % to 0.6 wt % of the ophthalmic atropine composition.
16. The composition of claim 1 , wherein the low dose atropine or pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of between 0.001 wt % and 0.01 wt %, and wherein the ophthalmic atropine composition has a pH of between 5.3 and 6.0.
17. The composition of claim 1 , wherein the low dose atropine or 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 ophthalmic atropine composition further comprises a chelator in an amount of 0.01 wt % or less of the ophthalmic atropine composition, and wherein the ophthalmic atropine composition has a pH of between 5.3 and 6.0.
18. The composition of claim 1 , wherein the composition further comprises a chelator in an amount of 0.01 wt % or less of the ophthalmic atropine composition, wherein the ophthalmic atropine composition has a pH of between 5.3 and 6.0, wherein the tonicity agent is present in the ophthalmic atropine composition in an amount of between 0.3 wt % and 0.7 wt %, and wherein the cellulosic viscosity modifier is present in an amount of between 0.4wt % and 0.6 wt % of the ophthalmic atropine composition.
19. The composition of claim 1 , wherein the composition comprises no deuterated water.
20. The composition of claim 17 , wherein the composition comprises no deuterated water.