Abuse-deterrent dosage forms containing esketamine

Patent metadata

Field	Value
Publication number	US-12589083-B2
Application number	US-202117523193-A
Country	US
Kind code	B2
Filing date	Nov 10, 2021
Priority date	May 7, 2019
Publication date	Mar 31, 2026
Grant date	Mar 31, 2026

Abstract

Disclosed herein are immediate release oral dosage forms that contain abuse-deterrent and abuse-resistant features. In particular, the disclosed dosage forms can provide deterrence of abuse by ingestion of multiple individual doses. The disclosed dosage forms can likewise provide protection from overdose in the event of accidental or intentional ingestion of multiple individual doses. The dosage forms may also exhibit abuse resistant properties when physically manipulated, and also when physically manipulated and then administered in a manner not consistent with oral dosing. The dosage forms may also exhibit abuse resistant properties when administered in a manner intended to result in administration of the esketamine in a higher than therapeutic dose.

First claim

What is claimed:

1 . A method of treating depression comprising orally administering to a subject in need thereof, an immediate release tablet comprising esketamine or a pharmaceutically acceptable salt thereof, sodium bicarbonate in an amount of no more than 2.2 wt % and 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one in an amount that is no more than 5.5 wt % after storage in accelerated conditions for at least 6 months.

2 . The method of claim 1 , wherein the immediate release tablet comprises between 5 and 100 mg of esketamine or a pharmaceutically acceptable salt thereof.

3 . The method of claim 1 , wherein the immediate release tablet comprises 40 mg base equivalent of esketamine.

4 . The method of claim 1 , wherein the immediate release tablet comprises between 20 mg and 100 mg of esketamine.

5 . The method of claim 4 , wherein prior to the administration, the immediate release tablet has been exposed to a storage period of six months;
after the storage period, the area under a peak corresponding to 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one present in the tablet is measured by high performance liquid chromatography (HPLC); and the total amount of 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one present in the tablet is determined to be no more than 5.5 wt. %; wherein the peak corresponding to 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one appears at a relative retention time of about 1.3 minutes when using C18, 100×3.0 mm, 3.5 μm HPLC column at a temperature of 45° C. and a sample temperature of 4° C., with a mobile phase comprising 0.050% trifluoroacetic acid (TFA) in water and 0.0025% TFA in acetonitrile and UV detection at 215 nm.

6 . The method of claim 5 , wherein the tablet is exposed to 40° C.±2° C. and 75%±5% relative humidity for the six month storage period.

7 . The method of claim 5 , wherein the tablet comprises 40-60 mg of esketamine.

8 . The method of claim 5 , wherein the tablet comprises 60 mg of esketamine.

9 . The method of claim 5 , wherein the 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one is measured in an amount of no more than 0.2 wt % after the storage period.

10 . The method of claim 5 , wherein the 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one is measured in a non-detectable amount after the storage period.

11 . The method according to claim 1 , wherein the immediate release tablet comprises sodium bicarbonate in an amount of no more than 2 wt %.

Assignees

• Clexio Biosciences Ltd

Inventors

• Moe Derek
• Seburg Randal
• Rane Sagar

Classifications

• G01N2030/027

  Liquid chromatography · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• A61K9/2009

  Inorganic compounds · CPC title

• A61K9/2027

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K9/2013

  Organic compounds, e.g. phospholipids, fats · CPC title