Emulsion formulations of an NK-1 receptor antagonist and uses thereof
Disclosed herein are novel pharmaceutical formulations of a neurokinin-1 (NK-1) receptor antagonist suitable for parenteral administration including intravenous administration. Also included are formulations including both the NK-1 receptor antagonist and dexamethasone sodium phosphate. The pharmaceutical formulations are stable oil-in-water emulsions for non-oral treatment of emesis and are particularly useful for treatment of subjects undergoing highly emetogenic cancer chemotherapy.
1. An injectable pharmaceutical emulsion comprising:
a neurokinase-1 (NK-1) receptor antagonist;
an emulsifier;
an oil;
a co-surfactant; and
an aqueous phase,
wherein the ratio of the emulsifier to the NK-1 receptor antagonist ranges from about 18:1 to 22:1 (wt/wt %).
2. The emulsion according to claim 1 , wherein the ratio of the oil to the NK-1 receptor antagonist ranges from about 5:1 to 15:1 (wt/wt %).
3. The emulsion according to claim 1 , wherein the ratio of the oil to the NK-1 receptor antagonist ranges from about 10:1 to 15:1 (wt/wt %).
4. The emulsion according to claim 1 , wherein the aqueous phase comprises water and a tonicity agent.
5. The emulsion according to claim 4 , wherein the aqueous phase further comprises a pH modifying agent.
6. The emulsion according to claim 1 , wherein the ratio of emulsifier to oil ranges from about 1:1 to 3:1 (wt/wt %).
7. The emulsion according to claim 1 , wherein the emulsifier is a phospholipid.
8. The emulsion according to claim 1 , wherein the emulsifier is an egg lecithin.
9. The emulsion according to claim 1 , further comprising dexamethasone sodium phosphate, wherein the dexamethasone sodium phosphate is present in the aqueous phase.
10. The emulsion according to claim 1 , wherein the NK-1 receptor antagonist is selected from the group consisting of rolapitant, netupitant, ezlopitant, vestipitant, serlopitant, maropitant, casopitant, befetupitant, and orvepitant.
11. The emulsion according to claim 5 , wherein the pH modifier is an oleate or a salt thereof.
12. The emulsion according to claim 5 , wherein the pH modifier is a buffer.
13. The emulsion according to claim 12 , wherein the buffer is Tris buffer.
14. The emulsion according to claim 1 , wherein the oil is soybean oil.
15. The emulsion according to claim 1 , wherein the co-surfactant comprises an alcohol.
16. The emulsion according to claim 1 , wherein the co-surfactant is ethanol.
17. The emulsion according to claim 16 , wherein the ethanol is present in the emulsion at less than 10 wt/wt %.
18. The emulsion according to claim 1 , wherein the NK-1 receptor antagonist is not aprepitant.