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 ophthalmic atropine composition, comprising:
an aqueous solution comprising low-dose atropine or a pharmaceutically acceptable salt thereof, a low-strength buffer, and a pharmaceutically acceptable tonicity agent;
wherein the low-strength buffer has a concentration of equal or less than 50 mM, and wherein the low-dose atropine is present at a concentration of equal or less than 0.05 wt %;
wherein the ophthalmic atropine composition has an acidic pH of equal or less than 6.0;
wherein the ophthalmic atropine composition contains not more than 0.01 wt % of a preservative; and
wherein the ophthalmic atropine composition has, after storage for two months at 25° C. and 60% relative humidity, equal or less than 0.35% tropic acid formed from degradation of the atropine.
2. The composition of claim 1 , wherein the low-dose atropine is present at a concentration of equal or less than 0.01 wt %.
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 between 0.01% and 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 between 0.001 wt % and 0.01 wt %.
5. The composition of claim 1 , wherein the atropine or a pharmaceutically acceptable salt thereof is atropine sulfate.
6. The composition of claim 1 , wherein the low-strength buffer comprises a first and a second buffer component.
7. The composition of claim 6 , wherein the low-strength buffer comprises monobasic and dibasic sodium phosphate.
8. The composition of claim 1 , wherein the ophthalmic atropine composition has a pH of between 4.5 and 6.0.
9. The composition of claim 1 , wherein the ophthalmic atropine composition has a pH of between about 5.0 and about 6.0.
10. The composition of claim 1 , further comprising a chelator.
11. The composition of claim 10 , wherein the chelator is present in an amount of about 0.01 wt %.
12. The composition of claim 10 , wherein the chelator is selected from the group consisting of a bicarboxylic acid, a tricarboxylic acid, and an aminopolycarboxylic acid.
13. The composition of claim 12 , wherein the chelator is EDTA.
14. The composition of claim 1 , wherein the pharmaceutically acceptable tonicity agent is glycerol, thioglycerol, mannitol, lactose, or dextrose.
15. The composition of claim 1 , wherein the pharmaceutically acceptable tonicity agent is a pharmaceutically acceptable salt that is present in the ophthalmic atropine composition in an amount of between 0.2 wt % and 0.8 wt %.
16. The composition of claim 1 , wherein the ophthalmic atropine composition has a viscosity of equal or less than about 20 cPs.
17. The composition of claim 1 , wherein the ophthalmic atropine composition has, after storage for two months at 25° C. and 60% relative humidity, equal or less than 0.30% tropic acid formed from degradation of the atropine.
18. 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 low-strength buffer comprises monobasic and dibasic sodium phosphate, and wherein the ophthalmic atropine composition has a pH of between 4.5 and 6.0.
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 ophthalmic atropine composition further comprises a chelator in an amount of 0.01 wt % +/−20% abs, of the ophthalmic atropine composition, and wherein the ophthalmic atropine composition has a pH of between 5.0 and 6.0.
20. The composition of claim 1 , wherein the low-strength buffer comprises monobasic and dibasic sodium phosphate, wherein the composition further comprises a chelator in an amount of about 0.01 wt % of the ophthalmic atropine composition, wherein the ophthalmic atropine composition has a pH of between about 5.0 and about 6.0, wherein the salt is present in the ophthalmic atropine composition in an amount of 0.5 wt % +/−0.2 wt %.