Emulsion formulations of an NK-1 receptor antagonist and uses thereof
View Patent ↗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. A method for treating a subject, comprising administering to the subject an injectable pharmaceutical emulsion, wherein the emulsion comprises:
a neurokinase-1 (NK-1) receptor antagonist;
11 wt/wt % to 15 wt/wt % of an emulsifier;
an oil;
a co-surfactant which comprises an alcohol;
a tonicity agent;
a pH modifier; and
water;
wherein the pH of the emulsion ranges from about 7.5 to 9.0, and the ratio of the emulsifier to the NK-1 receptor antagonist ranges from about 18:1 to 22:1 (wt/wt %), and wherein the subject is at risk of or is suffering from nausea and/or vomiting.
2. The method 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 method 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 method according to claim 1 , wherein the ratio of emulsifier to oil ranges from about 1:1 to 3:1 (wt/wt %).
5. The method according to claim 1 , wherein the emulsifier is a phospholipid.
6. The method according to claim 1 , wherein the emulsifier is an egg lecithin.
7. The method according to claim 1 , wherein the emulsion further comprises dexamethasone sodium phosphate, wherein the dexamethasone sodium phosphate is present in the aqueous phase.
8. The method 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.
9. The method according to claim 1 , wherein the pH modifier is oleic acid or a salt thereof.
10. The method according to claim 1 , wherein the pH modifier is a buffer.
11. The method according to claim 10 , wherein the buffer is Tris buffer.
12. The method according to claim 1 , wherein the oil is soybean oil.
13. The method according to claim 1 , wherein the alcohol is ethanol.
14. The method according to claim 13 , wherein the ethanol is present in the emulsion at less than 10 wt/wt %.
15. The method according to claim 1 , wherein the NK-1 receptor antagonist is not aprepitant.
16. The method according to claim 1 , wherein the nausea and/or vomiting is induced by chemotherapy, surgery, or radiotherapy.