Non-aqueous liquid nimodipine compositions
Non-aqueous liquid compositions comprising nimodipine having improved stability over aqueous compositions comprising nimodipine are provided herein. Methods of improving neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms with the non-aqueous liquid compositions of the present invention are also detailed herein.
1. A non-aqueous liquid composition consisting essentially of (i) nimodipine as the only active ingredient; and (ii) solvent comprising ethanol, polyethylene glycol, and glycerol, wherein the ethanol is present in the composition in an amount from about 0.1% (w/v) to about 1% (w/v), wherein about 5% or less nimodipine degradation is observed over a period of at least three months when exposed to 40° C. and 75% relative humidity.
2. The composition of claim 1 , comprising from about 0.01% to about 1.5% nimodipine related compound A.
3. The composition of claim 1 , wherein the concentration of nimodipine is from about 3 mg/mL to about 10 mg/mL.
4. The composition of claim 1 , wherein the concentration of nimodipine is about 6 mg/mL.
5. The composition of claim 1 , wherein the concentration of nimodipine is about 12 mg/mL.
6. The composition of claim 1 , wherein nimodipine is present in an amount from about 10 mg to about 100 mg per dosage unit.
7. The composition of claim 1 , wherein nimodipine is present in an amount of about 60 mg per dosage unit.
8. A method of improving neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms comprising administering to a patient in need thereof an effective amount of a non-aqueous liquid composition of claim 1 .
9. The method of claim 8 , wherein the concentration of nimodipine in the composition is greater than about 3 mg/mL.
10. The method of claim 8 , wherein the concentration of nimodipine in the composition is greater than about 6 mg/mL.
11. The method of claim 8 , wherein the concentration of nimodipine in the composition is about 12 mg/mL.
12. The method of claim 8 , wherein nimodipine is present in the composition in an amount from about 10 mg to about 100 mg per dosage unit.
13. The method of claim 8 , wherein nimodipine is present in the composition in an amount of about 60 mg per dosage unit.
14. The method of claim 8 , wherein the composition is administered orally, via nasogastric tube or via gastric tube.
15. The method of claim 8 , wherein a first unit dose of the composition is administered within about 100 hours after the subarachnoid hemorrhage.
16. The method of claim 8 , wherein a unit dose of the composition is administered about every four hours.
17. The composition of claim 1 , wherein the nimodipine is present at a concentration of about 6 mg/mL.
18. The composition of claim 1 , further comprising one or more preservative.
19. The composition of claim 18 , wherein the preservative is selected from the group consisting of methylparaben, propylparaben, ethylparaben, butylparaben, isobutylparaben, isopropylparaben, benzylparaben, sodium salts of the referenced parabens, or mixtures thereof.
20. The composition of claim 19 , wherein the preservative is methylparaben.