Claims for Patent: 11,813,231

Summary for Patent: 11,813,231

Title:	Nasal formulations of metoclopramide
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.
Inventor(s):	Matthew J. D'Onofrio, David A. Gonyer, Shirish A. Shah, Stuart J. Madden
Assignee:	Evoke Pharma Inc
Application Number:	US17/366,829
Patent Claims:	1. An intranasal pharmaceutical composition having a pH of above about 4.5, comprising metoclopramide, or a pharmaceutically acceptable salt thereof, and either (1) benzalkonium chloride at a concentration of at least 0.025% (w/v) and up to about 0.05% (w/v) or (2) benzyl alcohol at a concentration of less than 1% (w/v); wherein the intranasal pharmaceutical composition exhibits less than about 2% average change in percent optical density (O.D.) per week per 200 mg/mL of metoclopramide when stored at a temperature of 40° C. and 75% relative humidity for at least about 4 weeks. 2. The intranasal pharmaceutical composition of claim 1, wherein the intranasal pharmaceutical composition is substantially free of any additional antioxidant. 3. The intranasal pharmaceutical composition of claim 1, wherein the intranasal pharmaceutical composition further comprises at least one member of the group consisting of a salt, EDTA, sorbitol, a sugar, and a flavoring agent. 4. The intranasal pharmaceutical composition of claim 1, wherein the intranasal pharmaceutical composition has a concentration of metoclopramide, or a pharmaceutically-acceptable salt thereof, of from about 20.0% (w/v) to about 30.0% (w/v). 5. The intranasal pharmaceutical composition of claim 1, wherein the intranasal pharmaceutical composition has an osmolality of from about 500 mOsm/kg to about 1400 mOsm/kg. 6. The intranasal pharmaceutical composition of claim 1, wherein the pharmaceutical 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, IVIES (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. 7. The intranasal pharmaceutical composition of claim 6, wherein the buffer comprises sodium acetate. 8. The intranasal pharmaceutical composition of claim 6, wherein the buffer comprises sodium citrate. 9. The intranasal pharmaceutical composition of claim 1, wherein the intranasal pharmaceutical composition comprises benzyl alcohol at a concentration of up to about 0.8% (w/v). 10. A method of treating a patient, comprising intranasally administering to the patient an effective amount of the intranasal pharmaceutical composition of claim 1. 11. The method of claim 10, wherein the patient has a disorder that is treatable with metoclopramide. 12. The method of claim 11, wherein the disorder that is treatable with metoclopramide is selected from the group consisting of gastroparesis, emesis, delayed emesis, and nausea. 13. The method of claim 10, wherein the patient is human. 14. The intranasal pharmaceutical composition of claim 1, wherein the intranasal pharmaceutical composition is contained in a nasal administration device. 15. The intranasal pharmaceutical composition of claim 14, wherein the nasal administration device is adapted to deliver a pre-defined dose of the intranasal pharmaceutical composition to a nostril of a patient. 16. The intranasal pharmaceutical composition of claim 1, wherein the intranasal pharmaceutical composition comprises benzalkonium chloride at a concentration of from 0.025% to about 0.04% (w/v). 17. The intranasal pharmaceutical composition of claim 16, wherein the intranasal pharmaceutical composition comprises benzalkonium chloride at a concentration of from 0.025% to about 0.03% (w/v). 18. The intranasal pharmaceutical composition of claim 1, wherein the intranasal pharmaceutical composition comprises benzalkonium chloride at a concentration of 0.025% (w/v). 19. The intranasal pharmaceutical composition of claim 9, wherein the intranasal pharmaceutical composition comprises benzyl alcohol at a concentration of about 0.01% to about 0.1% (w/v). 20. The intranasal pharmaceutical composition of claim 19, wherein the intranasal pharmaceutical composition comprises benzyl alcohol at a concentration of about 0.75% (w/v).