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 low-strength buffer, a pharmaceutically acceptable salt, and a non-cellulosic viscosity modifier;
wherein the low-strength buffer has a concentration of equal or less than 50 mM, and 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 non-cellulosic viscosity modifier is present in the ophthalmic atropine composition to produce a dynamic viscosity of between 5 and 50 cP;
wherein the ophthalmic atropine composition has a pH of between 5.0 and 6.2; and
wherein the ophthalmic atropine composition, 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 non-cellulosic viscosity modifier is a polymeric compound, a polysaccharidic polymer, or glycerol.
3. The composition of claim 1 , wherein the non-cellulosic viscosity modifier is present in the ophthalmic atropine composition to produce a dynamic viscosity of between 10 and 30 cP.
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 atropine or pharmaceutically acceptable salt thereof is present in the ophthalmic atropine composition in an amount of between 0.01% and 0.02 wt %.
6. The composition of claim 1 , wherein the 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 atropine or pharmaceutically acceptable salt thereof is atropine sulfate.
8. The composition of claim 1 , wherein the low-strength buffer comprises a first and a second buffer component.
9. The composition of claim 1 , wherein the low-strength buffer has a concentration of between 0 mM and 20 mM.
10. The composition of claim 1 , wherein the ophthalmic atropine composition has a pH of between 5.0 and 6.0.
11. The composition of claim 1 , wherein the ophthalmic atropine composition has a pH of between 5.3 and 6.2.
12. The composition of claim 1 , further comprising a chelator.
13. The composition of claim 12 , wherein the chelator is present in an amount of between 0.008 wt % and 0.012 wt %.
14. The composition of claim 12 , wherein the chelator is selected from the group consisting of a bicarboxylic acid, a tricarboxylic acid, and an aminopolycarboxylic acid.
15. The composition of claim 1 , wherein the pharmaceutically acceptable salt 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 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 low-strength buffer comprises monobasic and dibasic sodium phosphate, and wherein the ophthalmic atropine composition has a pH of between 5.3 and 6.2.
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 between 0.008 wt % and 0.012 wt % of the ophthalmic atropine composition, and wherein the ophthalmic atropine composition has a pH of between 5.3 and 6.2.
18. 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 between 0.008 wt % and 0.012 wt % of the ophthalmic atropine composition, wherein the ophthalmic atropine composition has a pH of between 5.3 and 6.2, wherein the pharmaceutically acceptable salt is present in the ophthalmic atropine composition in an amount of between 0.3 wt % and 0.7 wt %, and wherein the non-cellulosic viscosity modifier is present in the ophthalmic atropine composition to produce a dynamic viscosity of between 10 cP and 30 cP.
19. The composition of claim 1 , wherein the composition comprises no deuterated water.
20. The composition of claim 16 , wherein the composition comprises no deuterated water.