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 liquid low-dose atropine ophthalmic formulation, comprising:
water as a pharmaceutical carrier in which are contained:
(a) atropine sulfate monohydrate in an amount of 0.1 mg/mL or 0.2 mg/mL or 0.5
mg/mL of the ophthalmic formulation;
(b) anhydrous monobasic sodium phosphate in an amount of 0.295 mg/mL of the
ophthalmic formulation;
(c) anhydrous dibasic sodium phosphate in an amount of 5.75 mg/mL of the
ophthalmic formulation;
(d) ethylenediaminetetraacetic acid (EDTA) in an amount of 0.1 mg/mL of the
ophthalmic formulation;
(e) sodium chloride in an amount of 5.0 mg/mL of the ophthalmic formulation;
(f) hypromellose 2910 in an amount of 5.0 mg/mL of the ophthalmic formulation;
and
(g) hydrochloric acid and/or sodium hydroxide in an amount sufficient to adjust a pH of the ophthalmic formulation;
wherein the pH of the ophthalmic formulation is between 5.0 and 6.0, and wherein the formulation is storage stable such that equal or less than 0.35% tropic acid is formed from degradation of the atropine upon storage over at least two months at 25° C. and 60% relative humidity.
2. The low-dose atropine ophthalmic formulation of claim 1 wherein the atropine sulfate monohydrate is present in an amount of 0.1 mg/mL of the ophthalmic formulation.
3. The low-dose atropine ophthalmic formulation of claim 1 wherein the atropine sulfate monohydrate is present in an amount of 0.2 mg/mL of the ophthalmic formulation.
4. The low-dose atropine ophthalmic formulation of claim 1 wherein the atropine sulfate monohydrate is present in an amount of 0.5 mg/mL of the ophthalmic formulation.
5. The low-dose atropine ophthalmic formulation of claim 1 wherein the pH is between 5.5+/−0.2 and 5.8+/−0.2.
6. The low-dose atropine ophthalmic formulation of claim 1 wherein the pH is 5.5+/−0.3.
7. The low-dose atropine ophthalmic formulation of claim 1 wherein the formulation is sterile.
8. The low-dose atropine ophthalmic formulation of claim 1 wherein the formulation is substantially free of preservatives.
9. A storage stable liquid low-dose atropine ophthalmic formulation, essentially consisting of:
water as a pharmaceutical carrier in which are contained:
(a) atropine sulfate monohydrate in an amount of 0.1 mg/mL or 0.2 mg/mL or 0.5
mg/mL of the ophthalmic formulation;
(b) anhydrous monobasic sodium phosphate in an amount of 0.295 mg/mL of the
ophthalmic formulation;
(c) anhydrous dibasic sodium phosphate in an amount of 5.75 mg/mL of the
ophthalmic formulation;
(d) ethylenediaminetetraacetic acid (EDTA) in an amount of 0.1 mg/mL of the
ophthalmic formulation;
(e) sodium chloride in an amount of 5.0 mg/mL of the ophthalmic formulation;
(f) hypromellose 2910 in an amount of 5.0 mg/mL of the ophthalmic formulation;
and
(g) hydrochloric acid and/or sodium hydroxide in an amount sufficient to adjust a pH of the ophthalmic formulation;
wherein the pH of the ophthalmic formulation is between 5.0 and 6.0, and wherein the formulation is storage stable such that equal or less than 0.35% tropic acid is formed from degradation of the atropine upon storage over at least two months at 25° C. and 60% relative humidity.
10. The low-dose atropine ophthalmic formulation of claim 9 wherein the atropine sulfate monohydrate is present in an amount of 0.1 mg/mL of the ophthalmic formulation.
11. The low-dose atropine ophthalmic formulation of claim 9 wherein the atropine sulfate monohydrate is present in an amount of 0.2 mg/mL of the ophthalmic formulation.
12. The low-dose atropine ophthalmic formulation of claim 9 wherein the atropine sulfate monohydrate is present in an amount of 0.5 mg/mL of the ophthalmic formulation.
13. The low-dose atropine ophthalmic formulation of claim 9 wherein the pH is between 5.5+/−0.2 and 5.8+/−0.2.
14. The low-dose atropine ophthalmic formulation of claim 9 wherein the pH is 5.5+/−0.3.
15. The low-dose atropine ophthalmic formulation of claim 9 wherein the formulation is sterile.
16. The low-dose atropine ophthalmic formulation of claim 9 wherein the formulation is substantially free of preservatives.
17. A container holding a low-dose atropine ophthalmic formulation according to claim 1 or claim 9 .
18. The container of claim 17 , wherein the container is configured as a single-use container.
19. The container of claim 17 , wherein the container is configured as a multi-dose container.
20. The container of claim 17 , wherein the container is covered with a secondary packaging system.