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 syringe containing a non-aqueous liquid composition comprising:
nimodipine as the only active ingredient wherein the concentration of nimodipine is about 6 mg/mL; and
one or more solvents selected from ethanol, isopropanol, butanol, isobutanol, glycerin, and polyethylene glycol;
wherein the non-aqueous liquid composition comprises less than 1% water by volume;
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 syringe containing the non-aqueous liquid composition of claim 1 , wherein the one or more solvents is a mixture of ethanol, glycerin, and polyethylene glycol.
3. The syringe containing the non-aqueous liquid composition of claim 1 , wherein one or more solvents is a mixture of polyethylene glycol and glycerin.
4. The syringe containing the non-aqueous liquid composition of claim 2 , wherein the one or more solvents is a mixture of polyethylene glycol, glycerin and isobutanol.
5. The syringe containing the non-aqueous liquid composition of claim 2 , wherein the one or more solvents is a mixture of polyethylene glycol, glycerin and butanol.
6. The syringe containing the non-aqueous liquid composition of claim 1 , wherein nimodipine is present in an amount from about 10 mg to about 100 mg.
7. The syringe containing the non-aqueous liquid composition of claim 6 , wherein nimodipine is present in an amount of about 60 mg per dosage unit.
8. The syringe containing the non-aqueous liquid composition of claim 1 , 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.
9. The syringe containing the non-aqueous liquid composition of claim 6 , wherein the nimodipine is present in an amount of about 30 mg per dosage unit.
10. The syringe containing the non-aqueous liquid composition of claim 6 , wherein the non-aqueous liquid composition comprises about 1 mL to about 20 mL of the one or more solvents per dosage unit.
11. The syringe containing the non-aqueous liquid composition of claim 6 , wherein the non-aqueous liquid composition comprises about 5 mL of the one or more solvents per dosage unit.
12. The syringe containing the non-aqueous liquid composition of claim 6 , wherein the non-aqueous liquid composition comprises about 10 mL of the one or more solvents per dosage unit.
13. The syringe containing the non-aqueous liquid composition of claim 1 , wherein the non-aqueous liquid composition further comprises a preservative.
14. The syringe containing the non-aqueous liquid composition of claim 13 , wherein the preservative is a paraben, a sorbate, a benzoate, sulfur dioxide, sulfite, nitrite, nitrate, lactic acid, propionic acid, propionate, ascorbic acid, ascorbate, butylated hydroxytoluene, or any combinations thereof.
15. The syringe containing the non-aqueous liquid composition of claim 14 , wherein the paraben is methylparaben, propylparaben, ethylparaben, butylparaben, isobutylparaben, isopropylparaben, benzylparaben, or any combinations thereof.
16. The syringe containing the non-aqueous liquid composition of claim 1 , comprising from about 0.01% to about 1.5% nimodipine related compound A.