Immediate release abuse-deterrent granulated dosage forms

Abstract

Described are immediate release oral dosage forms that contain abuse-deterrent features. In particular, the disclosed dosage forms provide deterrence of abuse by ingestion of multiple individual doses. In addition, the disclosed dosage forms provide protection from overdose in the event of accidental or intentional ingestion of multiple individual doses.

What is claimed: 
     
         1 . A method of treating depression comprising administering to a subject in need thereof a compressed tablet comprising 28 to 84 mg of esketamine or a pharmaceutically acceptable salt thereof, wherein the tablet comprises:
 0.1 to 25 wt % of a first polymeric component having an average molecular weight of less than 50,000 and selected from the group consisting of alginic acid, sodium carboxymethylcellulose, microcrystalline cellulose, dextrin, ethylcellulose, gelatin, starch, pregelatinized starch, polyvinyl alcohol, polyethylene oxide, polyvinylpyrrolidone, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, methylcellulose, hydroxypropyl cellulose, hydroxymethyl cellulose and any combination thereof;   1 to 10 wt % of a second polymeric component selected from the group consisting of a natural starch, a synthetic starch, a natural cellulose, a synthetic cellulose, an acrylate, a polyalkylene oxide, a carbomer and combinations thereof;   wherein dissolution or dispersion of the second polymeric component in water at a dry material concentration of 2% w/w creates a solution or dispersion with a viscosity of from about 100 to about 200,000 mPa s as evaluated at 20° C. and using the analysis method described in the USP 33 monograph for hypromellose; and   wherein not less than 75% of the esketamine, or pharmaceutically acceptable salt thereof, is released in 30 minutes, and wherein the release profile is evaluated by dissolution in 300 mL of 0.1N HCl media using USP II apparatus at 50 RPM paddle speed and 37° C.   
     
     
         2 . The method of  claim 1 , comprising 0.5 to 7 wt % of the first polymeric component. 
     
     
         3 . The method of  claim 1 , wherein the first polymeric component has an average molecular weight of less than 30,000. 
     
     
         4 . The method of  claim 1 , wherein the first polymeric component has an average molecular weight of less than 10,000. 
     
     
         5 . The method of  claim 1 , wherein the first polymeric component is water soluble. 
     
     
         6 . The method of  claim 1 , wherein the second polymeric component is selected from the group consisting of ethylcellulose, cellulose acetate, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate, cellulose ether, cellulose ester, cellulose ester ether, cellulose, hydroxypropyl methyl cellulose, hydroxy methyl cellulose, methyl cellulose, hydroxyethylmethyl cellulose, sodium carboxymethyl cellulose, a carbomer polymer, polyethylene oxide, and combinations thereof. 
     
     
         7 . The method of  claim 6 , wherein the second polymeric component comprises polyethylene oxide of average molecular weight between 100,000 and 7,000,000, hydroxypropyl methyl cellulose of average molecular weight between 10,000 and 1,500,000, hydroxypropyl cellulose of average molecular weight between 40,000 and 1,150,000, sodium carboxymethylcellulose of average molecular weight between 49,000 and 725,000, hydroxyethylcellulose of average molecular weight between 90,000 and 1,300,000, polyacrylic acid of average molecular weight between 80,000 and 200,000 or carbomer polymers of average molecular weight between 700,000 and 3,000,000,000. 
     
     
         8 . The method of  claim 1 , wherein the compressed tablet comprises about 28 mg of esketamine or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 1 , wherein the compressed tablet comprises about 56 mg of esketamine or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The method of  claim 1 , wherein the compressed tablet comprises about 84 mg of esketamine or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 1 , wherein the administration of the compressed tablet to the subject in need thereof reduces the potential for abuse of esketamine or a pharmaceutically acceptable salt thereof. 
     
     
         12 . The method of  claim 1 , wherein the administration reduces the risk of abuse of esketamine or a pharmaceutically acceptable salt thereof by simultaneous oral ingestion of multiple units of the compressed tablet. 
     
     
         13 . The method according to  claim 1 , wherein the administration reduces the risk of abuse of esketamine or a pharmaceutically acceptable salt thereof by nasal insufflation. 
     
     
         14 . The method according to  claim 1 , wherein the administration reduces the risk of abuse of esketamine or a pharmaceutically acceptable salt thereof by injection. 
     
     
         15 . A method of treating depression comprising administering to a subject in need thereof a compressed tablet comprising 28 to 84 mg of esketamine or a pharmaceutically acceptable salt thereof, wherein the tablet comprises;
 0.1 to 25 wt % of a first polymeric component having an average molecular weight of less than 50,000 and selected from the group consisting of alginic acid, sodium carboxymethylcellulose, microcrystalline cellulose, dextrin, ethylcellulose, gelatin, starch, pregelatinized starch, polyvinyl alcohol, polyethylene oxide, polyvinylpyrrolidone, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, methylcellulose, hydroxypropyl cellulose, hydroxymethyl cellulose and any combination thereof;   at least one second polymeric component of which each is selected from the group consisting of a natural starch, a synthetic starch, a natural cellulose, a synthetic cellulose, an acrylate, a polyalkylene oxide, and a carbomer, and wherein at least one of said polymeric components is present in the compressed tablet in an amount of 1 to 10 wt %;   wherein dissolution or dispersion of the at least one second polymeric component in water at a dry material concentration of 2% w/w creates a solution or dispersion with a viscosity of from about 100 to about 200,000 mPa s as evaluated at 20° C. and using the analysis method described in the USP 33 monograph for hypromellose; and   wherein not less than 75% of the esketamine, or pharmaceutically acceptable salt thereof, is released in 30 minutes, and wherein the release profile is evaluated by dissolution in 300 mL of 0.1N HCl media using USP II apparatus at 50 RPM paddle speed and 37° C.   
     
     
         16 . The method of  claim 15 , wherein the compressed tablet comprises no more than 90 wt % of second polymeric components. 
     
     
         17 . The method of  claim 15 , wherein the compressed tablet comprises no more than 20 wt % of second polymeric components. 
     
     
         18 . The method of  claim 15 , wherein the first polymeric component has an average molecular weight of less than 30,000. 
     
     
         19 . The method of  claim 15 , wherein the one or more second polymeric components are selected from the group consisting of ethylcellulose, cellulose acetate, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate, cellulose ether, cellulose ester, cellulose ester ether, cellulose, hydroxypropyl methyl cellulose, hydroxy methyl cellulose, methyl cellulose, hydroxyethylmethyl cellulose, sodium carboxymethyl cellulose, a carbomer polymer, polyethylene oxide, and combinations thereof. 
     
     
         20 . The method of  claim 19 , wherein the one or more second polymeric components comprise polyethylene oxide of average molecular weight between 100,000 and 7,000,000, hydroxypropyl methyl cellulose of average molecular weight between 10,000 and 1,500,000, hydroxypropyl cellulose of average molecular weight between 40,000 and 1,150,000, sodium carboxymethylcellulose of average molecular weight between 49,000 and 725,000, hydroxyethylcellulose of average molecular weight between 90,000 and 1,300,000, polyacrylic acid of average molecular weight between 80,000 and 200,000 or carbomer polymers of average molecular weight between 700,000 and 3,000,000,000.