Claims for Patent: 11,103,452

Summary for Patent: 11,103,452

Title:	Tramadol hydrochloride solution
Abstract:	Disclosed herein is an analgesic solution for the treatment of pain comprising a pain-relieving effective amount of tramadol or a pharmaceutically acceptable salt thereof, a method of treating pain by administering said analgesic solution to a subject in need thereof, a kit that includes containers of the analgesic solution, and a dosing regimen for the analgesic solution.
Inventor(s):	H. Greg Thomas, Richard Levasseur, Jeffrey S. Kiel
Assignee:	Athena Bioscience LLC
Application Number:	US17/009,565
Patent Claims:	1. An aqueous oral solution comprising: (a) from about 4.5 mg/mL to about 5.5 mg/mL of tramadol hydrochloride as the sole active ingredient; (b) from about 4% w/v to about 10% w/v of propylene glycol; (c) from about 10% w/v to about 30% w/v of glycerin; (d) a sufficient amount of a buffer to maintain the pH of the oral solution from about 4.5 to about 5.5; (e) from about 0.01% w/v to about 0.2% w/v sucralose; (f) a flavoring agent in an amount of from about 0.1% w/v to about 5% w/v; (g) sodium benzoate in an amount of from about 0.1% w/v to about 1% w/v; and (h) water, wherein the solution is free or substantially free of polyethylene glycol. 2. An aqueous oral solution comprising: (a) about 5 mg/mL of tramadol hydrochloride as the sole active ingredient; (b) about 5% w/v of propylene glycol; (c) about 20% w/v of glycerin; (d) about 0.1% w/v of citric acid and about 0.2% w/v of trisodium citrate dihydrate; (e) about 0.07% w/v of sucralose; (f) a flavoring agent in an amount of from about 0.1% w/v to about 1% w/v; (g) about 0.375% w/v of sodium benzoate; and (h) water, wherein (i) the solution has a pH of from about 4.5 to about 5.5 and (ii) the solution is free of polyethylene glycol. 3. The aqueous oral solution of claim 1, wherein the solution has a pH of from about 4.8 to about 5.4. 4. The aqueous oral solution of claim 1, wherein the solution has a pH of 5.0 or 5.1. 5. The aqueous oral solution of claim 2, wherein the solution has a pH of from about 4.8 to about 5.4. 6. The aqueous oral solution of claim 2, wherein the solution has a pH of 5.0 or 5.1. 7. The aqueous oral solution of claim 1, wherein the amount of tramadol hydrochloride is about 5 mg/mL. 8. The aqueous oral solution of claim 1, wherein the amount of propylene glycol ranges from about 5% w/v to about 7% w/v. 9. The aqueous oral solution of claim 1, wherein the buffer is a citrate buffer. 10. The aqueous oral solution of claim 9, wherein the citrate buffer is present in an amount of from about 0.2% w/v to about 0.4% w/v. 11. The aqueous oral solution of claim 1, wherein the sucralose is present in an amount of about 0.1% w/v. 12. The aqueous oral solution of claim 1, wherein the flavoring agent is grape flavor and present in an amount of from about 0.2% w/v to about 0.4% w/v. 13. The aqueous oral solution of claim 1, wherein the sodium benzoate is present in an amount of from about 0.3% w/v to about 0.4% w/v. 14. The aqueous oral solution of claim 1, wherein the solution exhibits an amount of tramadol hydrochloride of from about 0.45% w/v to about 0.55% w/v after storage at 25±2° C. and 40±5% relative humidity for 24 months. 15. The aqueous oral solution of claim 1, wherein the solution exhibits an amount of tramadol hydrochloride of from about 0.48% w/v to about 0.53% w/v after storage at 25±2° C. and 40±5% relative humidity for 24 months. 16. The aqueous oral solution of claim 1, wherein the solution exhibits an amount of tramadol hydrochloride of from about 0.49% w/v to about 0.51% w/v after storage at 25±2° C. and 40±5% relative humidity for 24 months. 17. The aqueous oral solution of claim 1, wherein the solution exhibits a tramadol maximum plasma concentration (Cmax) of from about 120 ng/mL to about 220 ng/mL and an 0-desmethyltramadol Cmax of from about 24 ng/mL to about 70 ng/mL following administration of the solution to an adult human under fasted conditions. 18. The aqueous oral solution of claim 1, wherein the solution exhibits a tramadol area under the curve in a plot of analyte concentration in blood plasma versus time from zero to infinity (AUC0-inf) of from about 825 hr*ng/mL to about 2445 hr*ng/mL and an 0-desmethyltramadol AUC0-inf of from about 370 hr*ng/mL to about 920 hr*ng/mL following administration of the solution to an adult human under fasted conditions; and wherein the solution is bioequivalent to an immediate release composition comprising tramadol when administered to an adult human under fasted conditions. 19. The aqueous oral solution of claim 1, wherein the solution is free or substantially free of non-ionic surfactants and/or co-solvents. 20. A method of treating pain in a subject in need thereof, which comprises administering to the subject an effective amount of the aqueous oral solution of claim 1.