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 liquid storage-stable low-dose ophthalmic atropine composition, comprising:
an aqueous solution comprising a buffer, a tonicity agent, a viscosity modifier, and atropine or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable salt hydrate thereof;
wherein the atropine or the pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof is present in the ophthalmic atropine composition in an amount of 0.01 wt %-0.05 wt %;
wherein the ophthalmic atropine composition has a pH of 3.5-6.0; 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 or pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof.
2. The composition of claim 1 , wherein the atropine or the pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof is atropine sulfate.
3. The composition of claim 1 , wherein the atropine or the pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof is atropine sulfate monohydrate.
4. The composition of claim 1 , wherein the buffer has a concentration of equal or less than 60 mM.
5. The composition of claim 1 , wherein the buffer comprises monobasic and dibasic sodium phosphate.
6. The composition of claim 1 , wherein the tonicity agent is a pharmaceutically acceptable salt.
7. The composition of claim 1 , wherein the viscosity modifier is a hydroxyethyl cellulose, a hydroxypropyl cellulose, or a hydroxypropyl methylcellulose.
8. The composition of claim 1 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.
9. The composition of claim 1 , wherein the atropine or a pharmaceutically acceptable salt thereof is atropine sulfate, 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 %.
10. The composition of claim 1 , wherein the ophthalmic atropine composition 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 or pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof.
11. The composition of claim 1 , wherein the ophthalmic atropine composition 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 or pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof.
12. The composition of claim 1 , wherein the atropine or pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof is present in the ophthalmic atropine composition in an amount of between 0.01% and 0.02 wt %.
13. The composition of claim 1 , wherein the ophthalmic atropine composition has an osmolality of 260-340 mOsm/kg.
14. The composition of claim 2 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.
15. The composition of claim 3 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.
16. The composition of claim 4 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.
17. The composition of claim 6 , wherein the salt is present in the ophthalmic atropine composition in an amount of between 0.2 wt % and 0.8 wt %.
18. The composition of claim 10 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.
19. The composition of claim 11 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.
20. The composition of claim 12 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.