Stable formulations for parenteral injection of small molecule drugs
Disclosed is a stable liquid formulation for parenteral injection comprising a biocompatible non-aqueous solvent and a small molecule drug, or a salt thereof, solubilized within the non-aqueous solvent, wherein the liquid formulation comprises less than 10% by weight residual water, and wherein the volume of the liquid formulation to be parenterally injected is from 0.1 μl to 3 ml.
1. A stable liquid formulation for parenteral injection comprising:
(a) a biocompatible non-aqueous aprotic solvent, wherein the non-aqueous aprotic solvent is dimethylsulfoxide (DMSO), dimethylformamide (DMF), ethyl acetate, n-methyl pyrrolidone (NMP), dimethyl acetamide (DMA), propylene carbonate, or mixtures thereof; and
(b) a small molecule drug, or a salt thereof, solubilized within the solvent, wherein the small molecule drug is selected from a catecholamine or a triptan, wherein the small molecule drug is present in the liquid formulation in an amount up to its solubility limit in the formulation;
wherein the liquid formulation comprises less than 5% by weight residual water; and
wherein the volume of the liquid formulation to be parenterally injected is 3 ml or less.
2. The stable liquid formulation of claim 1 , wherein the formulation is contained within a device for dispensing the liquid formulation.
3. The stable liquid formulation of claim 2 , wherein the device is a syringe, a pen injection device, an auto-injector device, a pump, or a perfusion bag.
4. The stable liquid formulation of claim 1 , wherein the volume of the liquid formulation to be parenterally injected is from 1 μl to 10 μl.
5. The stable liquid formulation of claim 1 , wherein the volume of the liquid formulation to be parenterally injected is from 10 μl to 1 ml.
6. The stable liquid formulation of claim 1 , wherein the volume of the liquid formulation to be parenterally injected is from 1 ml to 3 ml.
7. The stable liquid formulation of claim 1 , wherein the formulation for parenteral injection comprises 0.5 mg/ml to 700 mg/ml of small molecule drug.
8. The stable liquid formulation of claim 7 , wherein the non-aqueous aprotic solvent is DMSO, NMP, or a mixture thereof.
9. The stable liquid formulation of claim 1 , wherein the small molecule drug is a catecholamine.
10. The stable liquid formulation of claim 9 , wherein the catecholamine is epinephrine.
11. The stable liquid formulation of claim 10 , wherein the formulation for parenteral injection comprises 0.5 mg/ml to 700 mg/ml of epinephrine.
12. The stable liquid formulation of claim 11 , wherein the non-aqueous aprotic solvent is DMSO, NMP, or a mixture thereof.
13. A method of treating an allergic reaction, comprising parenterally injecting the stable liquid formulation of claim 10 to a subject in need thereof.
14. The stable liquid formulation of claim 1 , wherein the small molecule drug is a triptan.
15. The stable liquid formulation of claim 14 , wherein the triptan is sumatriptan.
16. A method of treating a migraine, comprising parenterally injecting the stable liquid formulation of claim 15 to a subject in need thereof.
17. The stable liquid formulation of claim 15 , wherein the formulation for parenteral injection comprises 0.5 mg/ml to 400 mg/ml of sumatriptan.
18. The stable liquid formulation of claim 17 , wherein the non-aqueous aprotic solvent is DMSO, NMP, or a mixture thereof.
19. A method comprising parenterally injecting the stable liquid formulation of claim 1 to a subject.
20. The method of claim 19 , wherein the stable liquid formulation is parenterally injected with a syringe, a pen injection device, an auto-injector device, a pump, or a perfusion bag.
21. The method of claim 19 , wherein the stable liquid formulation is not diluted prior to administration.