# US 10,500,208 B2 · Emulsion formulations of aprepitant > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,500,208 B2 - Document ID: US10500208B2 - Status: Granted - Kind: B2 - Application number: 15/398,928 - Filed: 2017-01-05 - Published: 2017-04-27 - Granted: 2019-12-10 - Earliest claimed: 2014-09-19 - Assignees: Heron Therapeutics, Inc. - Applicants: Heron Therapeutics, Inc. - Inventors: Thomas B. Ottoboni; Han Han - Web page: https://patentgrep.com/patent/US10500208B2 ## CPC - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)} - A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} - A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids - A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14) - A61P 1/08: for nausea, cinetosis or vertigo; Antiemetics - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Disclosed herein are novel pharmaceutical formulations of aprepitant suitable for parenteral administration including intravenous administration. Also included are formulations including both aprepitant 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. ## Claims ### Claim 1 An injectable emulsion comprising: aprepitant; 11 wt/wt % to 15 wt/wt % of an emulsifier; an oil; a co-emulsifier which is an alcohol; a tonicity modifier; a pH modifier; and water; wherein the pH of the emulsion ranges from about 7.5 to 9.0, wherein the emulsion is physically stable. ### Claim 2 (depends on 1) The emulsion according to claim 1, wherein the ratio of the oil to the aprepitant in the emulsion ranges from about 11:1 to 15:1 (wt/wt %). ### Claim 3 (depends on 1) The emulsion according to claim 1, wherein the ratio of the emulsifier to the aprepitant in the emulsion ranges from about 15:1 to 30:1 (wt/wt %). ### Claim 4 (depends on 1) The emulsion according to claim 1, wherein the ratio of emulsifier to oil ranges from about 1:1 to 3:1 (wt/wt %). ### Claim 5 (depends on 4) The emulsion according to claim 4, wherein the emulsifier is a phospholipid. ### Claim 6 (depends on 1) The emulsion according to claim 1, further comprising dexamethasone sodium phosphate, wherein the dexamethasone sodium phosphate is present in the aqueous phase. ### Claim 7 (depends on 1) The emulsion according to claim 1, wherein the emulsifier is an egg lecithin. ### Claim 8 (depends on 1) The emulsion according to claim 1, further comprising a buffer. ### Claim 9 (depends on 1) The emulsion according to claim 1, wherein the pH modifier is sodium oleate. ### Claim 10 (depends on 8) The emulsion according to claim 8, wherein the buffer is Tris buffer. ### Claim 11 (depends on 1) The emulsion according to claim 1, wherein the oil is soybean oil. ### Claim 12 (depends on 1) The emulsion according to claim 1, wherein the alcohol is ethanol. ### Claim 13 (depends on 12) The emulsion according to claim 12, wherein the ethanol is present at less than 10 wt/wt %. ### Claim 14 (depends on 1) A method for preparing a pharmaceutical emulsion according to claim 1 comprising: combining the aprepitant, the emulsifier, and the alcohol with the oil to generate an oil phase; combining water, the Tonicity agent, the pH modifier, and optionally the buffer to generate an aqueous phase; homogenizing, the oil phase with the aqueous phase to generate a coarse emulsion premix; homogenizing the coarse emulsion premix at a pressure between 10,000 and 30,000 psi using a microfluidizer to generate the pharmaceutical emulsion; and sterilizing the pharmaceutical emulsion. ### Claim 15 (depends on 14) The method according to claim 14, wherein homogenizing the coarse emulsion premix comprises 4 to 15 passes through the microfluidizer. ### Claim 16 (depends on 14) The method according to claim 14, wherein the sterilizing comprising passing the pharmaceutical emulsion through a filter having a pore size of about 0.2 microns. ### Claim 17 (depends on 14) The method according to claim 14, further comprising adding a solution of dexamethasone sodium phosphate to the fine emulsion prior to sterile filtration.