# US 2021/0330618 A1 · Nasal formulations of metoclopramide

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- Number: US 2021/0330618 A1
- Document ID: US20210330618A1
- Status: Published application
- Kind: A1
- Application number: 17/366,818
- Filed: 2021-07-02
- Published: 2021-10-28
- Earliest claimed: 2008-12-22
- Assignees: Evoke Pharma, Inc.
- Applicants: Evoke Pharma, Inc.
- Inventors: Matthew J. D'ONOFRIO; David A. GONYER; Shirish A. SHAH; Stuart J. MADDEN
- Web page: https://patentgrep.com/patent/US20210330618A1

## CPC

- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- A61K 9/0043: {Nose}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- 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
- A61M 11/02: operated by air {or other gas} pressure applied to the liquid {or other product} to be sprayed or atomised {(sprayers for horticulture A01G, A01H; killing insects A01M; air humidifying by nozzles F24F6/14, F24F6/18; cooling by spraying F28B, F28C)}
- C07C 237/44: having carbon atoms of carboxamide groups, amino groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- A61M 15/08: Inhaling devices inserted into the nose
- 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)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

Nasal formulations of metoclopramide, which remain stable and/or colorless upon storage over a period of time, are provided. Also provided are methods of treating disorders treatable with metoclopramide, comprising administering the nasal solutions to patients in need thereof.

## Claims

### Claim 1

A method of treating gastroparesis in a patient, comprising intranasally administering to the patient an amount of a metoclopramide composition effective to deliver a daily dose of about 30 mg of metoclopramide, or a pharmaceutically-acceptable salt thereof, to the patient, wherein the composition comprises citrate in a concentration of at least about 10 millimolar, and wherein the intranasally administering is effective to treat gastroparesis.

### Claim 2 (depends on 1)

The method of claim 1, wherein the intranasal administration comprises an intranasal spray.

### Claim 3 (depends on 2)

The method of claim 2, wherein the intranasal spray is administered as one, two, three, or four intranasal sprays per day.

### Claim 4 (depends on 1)

The method of claim 1, wherein the metoclopramide composition further comprises benzalkonium chloride.

### Claim 5 (depends on 4)

The method of claim 4, wherein the benzalkonium chloride is present in the metoclopramide composition at a concentration of from about 0.005% (w/v) to about 0.05% (w/v).

### Claim 6 (depends on 1)

The method of claim 1, wherein the metoclopramide composition has a pH of above about 4.5.

### Claim 7 (depends on 1)

The method of claim 1, wherein the metoclopramide composition further comprises benzyl alcohol.

### Claim 8 (depends on 1)

The method of claim 1, wherein the metoclopramide composition has an osmolality of from about 500 mOsm/kg to about 1400 mOsm/kg.

### Claim 9 (depends on 1)

The method of claim 1, wherein the metoclopramide composition further comprises a buffer selected from the group consisting of citric acid/phosphate, acetate, barbital, borate, Britton-Robinson, cacodylate, citrate, collidine, formate, maleate, McIlvaine, phosphate, Prideaux-Ward, succinate, citrate-phosphate-borate (Teorell-Stanhagen), veronal acetate, MES (2-(N-morpholino)ethanesulfonic acid), BIS-TRIS (bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane), ADA (N-(2-acetamido)-2-iminodiacetic acid), ACES (N-(carbamoylmethyl)-2-aminoethanesulfonaic acid), PIPES (piperazine-N,N′-bis(2-ethanesulfonic acid)), MOPSO (3-(N-morpholino)-2-hydroxypropanesulfonic acid), BIS-TRIS PROPANE (1,3-bis(tris(hydroxymethyl)methylamino)propane), BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonaic acid), MOPS (3-(N-morpholino)propanesulfonic acid), TES (N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid), HEPES (N-(2-hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid), DIPSO (3-(N,N-bis(2-hydroxyethyl)amino)-2-hydroxypropanesulfonic acid), MOBS (4-(N-morpholino)butanesulfonic acid), TAPSO (3-(N-tris(hydroxymethyl)methylamino)-2-hydroxy-propanesulfonic acid), tris(hydroxymethylaminomethane, HEPPSO(N-(2-hydroxyethyl)piperazine-N′-(2-hydroxypropanesulfonic acid), POPSO (piperazine-N,N′-bis(2-hydroxypropanesulfonic acid)), TEA (triethanolamine), EPPS(N-(2-hydroxyethyl)piperazine-N′-(3-propane-sulfonic acid), TWINE (N-tris(hydroxymethyl)methylglycine), GLY-GLY (glycylglycine), BICINE (N,N-bis(2-hydroxyethyl)glycine), HEPBS (N-(2-hydroxyethyl)piperazine-N′-(4-butanesulfonic acid)), TAPS(N-tris(hydroxy-methypmethyl-3-aminopropanesulfonic acid), or AMPD (2-amino-2-methyl-1,3 -propanediol) buffer.

### Claim 10 (depends on 9)

The method of claim 9, wherein the buffer comprises sodium acetate.

### Claim 11 (depends on 9)

The method of claim 9, wherein the buffer comprises sodium citrate.

### Claim 12 (depends on 1)

The method of claim 1, wherein the patient has a disorder that is treatable with metoclopramide.

### Claim 13 (depends on 12)

The method of claim 12, wherein the disorder that is treatable with metoclopramide is selected from the group consisting of gastroparesis, emesis, delayed emesis, and nausea.

### Claim 14 (depends on 7)

The method of claim 7, wherein the benzyl alcohol is present in the metoclopramide composition at a concentration from about 0.01% (w/v) to about 0.8% (w/v).

### Claim 15 (depends on 1)

The method of claim 1, wherein the metoclopramide composition further comprises at least one member of the group consisting of a salt, EDTA, sorbitol, a sugar, and a flavoring agent.

### Claim 16 (depends on 1)

The method of claim 1, wherein the patient is human.

### Claim 17 (depends on 1)

The method of claim 1, wherein the metoclopramide composition is substantially free of any additional antioxidant.