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 tonicity agent other than a pharmaceutically acceptable salt, and a 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 ophthalmic atropine composition has a pH of between 5.0 and 6.0; 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 tonicity agent is selected from the group consisting of glycerol, mannitol, lactose, and dextrose.
3. The composition of claim 1 , wherein the tonicity agent is glycerol.
4. The composition of claim 1 , wherein the tonicity agent is mannitol.
5. The composition of claim 1 , wherein the tonicity agent is present in the ophthalmic atropine composition in an amount sufficient to adjust osmolality of the formulation to a range of 260 to 340 mOsm/kg.
6. 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 %.
7. 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 %.
8. 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 %.
9. The composition of claim 1 , wherein the atropine or pharmaceutically acceptable salt thereof is atropine sulfate.
10. The composition of claim 1 , wherein the low-strength buffer comprises a first and a second buffer component.
11. The composition of claim 1 , wherein the low-strength buffer has a concentration of equal or less than 20 mM.
12. The composition of claim 1 , wherein the ophthalmic atropine composition has a pH of between 5.5 and 6.0.
13. The composition of claim 1 , further comprising a chelator.
14. The composition of claim 13 , wherein the chelator is present in an amount of between 0.008 wt % and 0.012 wt %.
15. The composition of claim 13 , wherein the chelator is selected from the group consisting of a bicarboxylic acid, a tricarboxylic acid, and an aminopolycarboxylic acid.
16. The composition of claim 1 , wherein the cellulosic viscosity modifier is a hydroxyethyl cellulose, a hydroxypropyl cellulose, or a hydroxypropyl methylcellulose.
17. The composition of claim 1 , wherein the cellulosic viscosity modifier is present in an amount of between 0.4 wt % and 0.6 wt % of the ophthalmic atropine composition.
18. 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 %, 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 6.0.
19. 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 %, 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 6.0.
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 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 6.0, wherein the tonicity agent is present in the ophthalmic atropine composition to adjust osmolality of the formulation to a range of 260 to 340 mOsm/kg, and wherein the cellulosic viscosity modifier is present in an amount of between 0.4 wt % and 0.6 wt % of the ophthalmic atropine composition.
21. The composition of claim 1 , wherein the composition comprises no deuterated water.
22. The composition of claim 20 , wherein the composition comprises no deuterated water.