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 or a pharmaceutically acceptable salt hydrate thereof, a tonicity agent, and a viscosity modifier, wherein the aqueous solution contains no buffer;
wherein the low-dose atropine or pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof is present at a concentration of 0.01-0.05 wt %;
wherein the pH of the ophthalmic atropine composition is 5.0-6.0; 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.
2 . 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.
3 . 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.
4 . The composition of claim 1 , wherein the low-dose 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 %.
5 . The composition of claim 1 , wherein the low-dose atropine or pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof is atropine sulfate.
6 . The composition of claim 1 , wherein the low-dose atropine or pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof is atropine sulfate monohydrate.
7 . The composition of claim 1 , wherein the tonicity agent is present in the ophthalmic atropine composition in an amount to adjust osmolality of the composition to 260-340 mOsm/kg.
8 . The composition of claim 1 , wherein the tonicity agent is sodium chloride and wherein sodium chloride is present in the ophthalmic atropine composition in an amount ranging from 0.3 wt % to 0.7 wt %.
9 . The composition of claim 1 , wherein the ophthalmic atropine composition has a viscosity of 1-30 cP.
10 . The composition of claim 1 , wherein the low-dose atropine or pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof is atropine.
11 . 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 0.28% tropic acid formed from degradation of the atropine or pharmaceutically acceptable salt thereof or pharmaceutically acceptable salt hydrate thereof.
12 . The composition of claim 7 , wherein the ophthalmic atropine composition has a viscosity of 1-30 cP.
13 . The composition of claim 1 , wherein the viscosity modifier is a hydroxyethyl cellulose, a hydroxypropyl cellulose, or a hydroxypropyl methylcellulose.
14 . The composition of claim 1 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.
15 . The composition of claim 2 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.
16 . The composition of claim 3 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.01 wt %.
17 . The composition of claim 1 , wherein the tonicity agent is a pharmaceutically acceptable salt.
18 . The composition of claim 1 , wherein the ophthalmic atropine composition does not comprise benzalkonium chloride, cetrimide or cetrimonium chloride or bromide, benzododecinium bromide, miramine, cetylpyridinium chloride, polidronium chloride, polyquaternium-1, polyquaternium-42, sepazonium chloride, or a phenylmercury salt.
19 . The composition of claim 1 , wherein the ophthalmic atropine composition does not comprise a preservative.
20 . The composition of claim 1 , wherein the ophthalmic atropine composition includes a preservative in an amount of no more than 0.005 wt %.