Immediate release abuse-deterrent granulated dosage forms
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.
1. An immediate release abuse deterrent oral dosage form comprising:
an active pharmaceutical ingredient that is ketamine, esketamine, or a pharmaceutically acceptable salt thereof;
a core comprising up to 10% by weight of the total amount of the active pharmaceutical ingredient;
wherein the dosage form demonstrates an immediate release profile of the active pharmaceutical ingredient when administered to a human in therapeutic doses, and an extended release profile of the active pharmaceutical ingredient when administered to a human in supratherapeutic doses, wherein the immediate release profile is defined as not less than 75% of API released in 30 minutes, and the extended release profile is defined as not more than 95% released in 60 minutes, and wherein the release profiles are 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 dosage form according to claim 1 , wherein at least one layer surrounds the core comprising a pH-sensitive polymer that is insoluble in water at a pH greater than 5.
3. The dosage form according to claim 2 , wherein the pH-sensitive polymer is a copolymer of dimethyl aminoethyl methacrylate, butyl methacrylate, and methyl methacrylate monomers.
4. The dosage form according to claim 1 , wherein the dosage form further comprises a gelling polymer.
5. The dosage form according to claim 4 , wherein the gelling polymer 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.
6. The dosage form according to claim 4 , wherein the gelling polymer in present in an amount from 0.7 to 20 weight percent based of the total weight of the dosage form.
7. The dosage form of claim 4 , wherein gelling polymer in present in an amount from 2 to 15 weight percent based of the total weight of the dosage form.
8. The dosage form of claim 4 , wherein the gelling polymer is present in the core in an amount from 2 to 15 weight percent of the total weight of the dosage form.
9. The dosage form of claim 4 , wherein the gelling polymer comprises 50 to 75 weight percent of the total weight of the core.
10. The dosage form according to claim 1 , wherein the core further comprises a wax that is selected from fatty acid esters, glycerol fatty acid esters, fatty alcohols, animal waxes, vegetable waxes, mineral waxes, petroleum waxes, synthetic waxes, or any mixture thereof.
11. The dosage form according to claim 10 , wherein the fatty alcohol is selected from glycerol behenate, glycerol palmitostearate, glycerol monostearate, and stearoyl macroglycerides.
12. The dosage form of claim 1 further comprising a disintegrant present in an amount of 1 to 30 weight percent of the total weight of the dosage form.
13. The dosage form according to claim 1 , wherein the dosage form is in a compressed tablet form.
14. The dosage form according to claim 1 , wherein less than 5% by weight of the total amount of the active pharmaceutical ingredient is contained in the core.
15. The dosage form according to claim 1 , wherein the supratherapeutic dose is five or more units of said dosage form.
16. A method of reducing the potential for abuse by a human of an active pharmaceutical ingredient comprising ketamine, esketamine, or a pharmaceutically acceptable salt thereof, the method comprising providing an oral immediate release abuse deterrent dosage form according to claim 1 .
17. The method according to claim 16 , wherein the dosage form reduces the risk of abuse of the active pharmaceutical ingredient by simultaneous oral ingestion of multiple unit of the oral dosage form.
18. The method according to claim 16 , wherein the dosage form reduces the risk of abuse of the active pharmaceutical ingredient by nasal insufflation.
19. The method according to claim 16 , wherein the dosage form reduces the risk of abuse of the active pharmaceutical ingredient by injection.
20. A method for treating a subject having depression, comprising administering to the subject a dosage form according to claim 1 .