Claims for Patent: 11,628,150

Summary for Patent: 11,628,150

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:	US17/100,664
Patent Claims:	1. A pharmaceutical composition formulated for intranasal administration, the pharmaceutical composition: comprising metoclopramide, or a pharmaceutically-acceptable salt thereof; having a pH of above about 4.5; providing 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; and comprising a citric acid buffer comprising a combination of citric acid monohydrate and sodium citrate dihydrate, wherein the combination provides a citrate concentration of at least 10 millimolar, and wherein the citric acid monohydrate is at a concentration of up to 50 millimolar. 2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition further comprises benzalkonium chloride. 3. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has a pH of at least about 4.6. 4. The pharmaceutical composition of claim 1, wherein the average change of percent optical density (O.D.) is less than about 1.8% O.D. per week. 5. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is contained in a nasal administration device. 6. The pharmaceutical composition of claim 1, wherein the citric acid monohydrate is in an amount of from about 0.2% to about 0.5% w/v, from about 0.25% to about 0.4% w/v, or from about 0.3% to about 0.35% w/v and the sodium citrate dihydrate is in an amount from about 1.0 to about 1.8% w/v, from about 1.2 to about 1.6% w/v, or from about 1.3 to about 1.5% w/v. 7. The pharmaceutical composition of claim 6, wherein the citric acid monohydrate is in an amount of less than 0.5% and the sodium citrate dihydrate is in an amount of less than 1.8% w/v. 8. The pharmaceutical composition of claim 7, wherein a combined amount of citric acid monohydrate and sodium citrate dihydrate in the pharmaceutical composition is less than 2.3% w/v. 9. The pharmaceutical composition of claim 1, wherein the citric acid monohydrate is in an amount of about 0.1% and the sodium citrate dihydrate is in an amount of about 0.44%. 10. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has a citric acid monohydrate concentration of about 5-50 millimolar. 11. A method of treating a patient having a disorder selected from the group consisting of gastroparesis, emesis, delayed emesis, and nausea, comprising intranasally administering to the patient an effective amount of the pharmaceutical composition of claim 1. 12. The method of claim 11, wherein the intranasal administration comprises an intranasal spray. 13. The method of claim 12, wherein the intranasal spray is administered as two sprays. 14. A pharmaceutical composition formulated for intranasal administration, the pharmaceutical composition comprising metoclopramide, or a pharmaceutically-acceptable salt thereof, and a citric acid buffer comprising a combination of citric acid monohydrate and sodium citrate dihydrate, wherein the combination provides a citrate concentration of at least 10 millimolar, and wherein the citric acid monohydrate is at a concentration of up to 50 millimolar; wherein the pharmaceutical composition does not discolor when stored at a temperature of 40° C. for at least about 4 weeks. 15. The pharmaceutical composition of claim 14, wherein the pharmaceutical composition further comprises benzalkonium chloride. 16. The pharmaceutical composition of claim 15, wherein the pharmaceutical composition has a concentration of benzalkonium chloride from about 0.005% (w/v) to about 0.05% (w/v). 17. The pharmaceutical composition of claim 14, wherein the pharmaceutical composition has a pH of above about 4.5. 18. The pharmaceutical composition of claim 14, wherein the pharmaceutical composition further comprises benzyl alcohol. 19. The pharmaceutical composition of claim 18, wherein the pharmaceutical composition comprises benzyl alcohol in a concentration from about 0.01% (w/v) to about 0.8% (w/v). 20. The pharmaceutical composition of claim 14, wherein the pharmaceutical composition has an osmolality of from about 500 mOsm/kg to about 1400 mOsm/kg. 21. The pharmaceutical composition of claim 14, wherein the citric acid monohydrate is in an amount of about 0.1% and the sodium citrate dihydrate is in an amount of about 0.44%. 22. The pharmaceutical composition of claim 14, wherein the pharmaceutical composition has a citric acid monohydrate concentration of about 5-50 millimolar. 23. The pharmaceutical composition of claim 14, wherein the pharmaceutical composition further comprises at least one member of the group consisting of a salt, EDTA, sorbitol, a sugar, and a flavoring agent. 24. The pharmaceutical composition of claim 14, wherein the pharmaceutical composition is contained in a nasal administration device. 25. The pharmaceutical composition of claim 14, wherein the citric acid monohydrate is in an amount of from about 0.2% to about 0.5% w/v, from about 0.25% to about 0.4% w/v, or from about 0.3% to about 0.35% w/v and the sodium citrate dihydrate is in an amount from about 1.0 to about 1.8% w/v, from about 1.2 to about 1.6% w/v, or from about 1.3 to about 1.5% w/v. 26. The pharmaceutical composition of claim 25, wherein the citric acid monohydrate is in an amount of less than 0.5% and the sodium citrate dihydrate is in an amount of less than 1.8% w/v. 27. The pharmaceutical composition of claim 26, wherein a combined amount of citric acid monohydrate and sodium citrate dihydrate in the pharmaceutical composition is less than 2.3% w/v. 28. A method of treating a patient having a disorder selected from the group consisting of gastroparesis, emesis, delayed emesis, and nausea, comprising intranasally administering to the patient an effective amount of the pharmaceutical composition of claim 14. 29. The method of claim 28, wherein the intranasal administration comprises an intranasal spray. 30. The method of claim 29, wherein the intranasal spray is administered as two sprays.