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 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 enterally administering to a patient in need thereof an effective amount of a non-aqueous liquid composition comprising (i) nimodipine as the only active ingredient and (ii) one or more solvents selected from the group consisting of polyethylene glycol, ethanol, isopropanol, butanol, and glycerin,
wherein the non-aqueous liquid composition (a) has a concentration of at least about 6 mg/mL, (b) comprises less than 1% water by volume, and (c) exhibits 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 method of claim 1 , wherein the polyethylene glycol is selected from PEG 300 and PEG 400.
3. The method of claim 1 , wherein polyethylene glycol comprises from about 50% to about 75% of the non-aqueous liquid composition.
4. The method of claim 1 , wherein the non-aqueous liquid composition comprises nimodipine, polyethylene glycol and glycerin.
5. The method of claim 1 , wherein the non-aqueous liquid composition comprises polyethylene glycol, glycerin and isobutanol.
6. The method of claim 1 , wherein the non-aqueous liquid composition comprises nimodipine, polyethylene glycol, glycerin and butanol.
7. The method of claim 1 , wherein the non-aqueous liquid composition comprises from about 0.01% to about 1.5% nimodipine related compound A.
8. The method of claim 1 , wherein nimodipine is present in the non-aqueous liquid composition in an amount from about 10 mg to about 100 mg per dosage unit.
9. The method of claim 1 , wherein the composition is administered orally, via nasogastric tube or via gastric tube.
10. The method of claim 1 , wherein the non-aqueous liquid composition is administered to the patient within about 100 hours of the subarachnoid hemorrhage.
11. The method of claim 1 , wherein the non-aqueous liquid composition is administered twice or more per day.
12. The method of claim 11 , wherein the non-aqueous liquid composition is administered every four hours.
13. The method of claim 1 , wherein the non-aqueous liquid composition is administered once per day.