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 liquid composition, comprising
(a) nimodipine as the only active ingredient, wherein the nimodipine is present in the liquid composition at a concentration of about 6 mg/mL;
(b) polyethylene glycol, wherein the polyethylene glycol is present in the liquid composition in an amount of about 60% to about 70% (w/v);
(c) glycerin, wherein the glycerin is present in the liquid composition in an amount of about 40% to about 50% (w/v);
wherein about 5% or less nimodipine degradation is observed over a period of at least six months when exposed to 40° C. and 75% relative humidity, and
wherein the liquid composition is formulated for enteral administration.
2. The liquid composition of claim 1 , further comprising ethanol.
3. The liquid composition of claim 2 , wherein the ethanol is 95% ethanol.
4. The liquid composition of claim 2 , wherein the ethanol is present in the liquid composition in an amount of about 1% or less by weight.
5. The liquid composition of claim 1 , further comprising water.
6. The liquid composition of claim 5 , wherein the water is present in the liquid composition in an amount of about 1% or less by volume.
7. The liquid composition of claim 1 , further comprising a buffer agent.
8. The liquid composition of claim 1 , further comprising a paraben preservative.
9. 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 the liquid composition of claim 1 .
10. The method of claim 9 , wherein the liquid composition is administered orally, via nasogastric tube or via gastric tube.
11. The method of claim 9 , wherein a first unit dose of the liquid composition is administered to the patient within about 100 hours of the subarachnoid hemorrhage.
12. The method of claim 9 , wherein the liquid composition is administered about every four hours.