Immediate release abuse-deterrent granulated dosage forms

Patent metadata

Field	Value
Publication number	US-10888528-B2
Application number	US-201916241102-A
Country	US
Kind code	B2
Filing date	Jan 7, 2019
Priority date	Dec 8, 2014
Publication date	Jan 12, 2021
Grant date	Jan 12, 2021

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.

First claim

What is claimed:

1. An immediate release abuse deterrent oral dosage form comprising:
core-shell particles that include
an active pharmaceutical ingredient that is ketamine, esketamine, or a pharmaceutically acceptable salt thereof;
a core comprising a gelling polymer and up to 10% by weight of the total amount of the active pharmaceutical ingredient in said core-shell particles;
an active pharmaceutical layer surrounding the core and comprising the active pharmaceutical ingredient; and,
at least one layer surrounding said active pharmaceutical layer, wherein the at least one layer comprises a pH-sensitive film comprising a pH-sensitive polymer that is insoluble in water at a pH greater than 5;

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, and,
wherein the dosage form resists attempted abuse of the active pharmaceutical ingredient by injection or nasal insufflation.

2. The dosage form according to claim 1 , further comprising a matrix comprising a disintegrant and a gelling polymer.

3. The dosage form according to claim 1 , wherein the dosage form is in a compressed tablet form.

4. The dosage form according to claim 1 , wherein less than 5% by weight of the total amount of the active pharmaceutical ingredient in the core-shell particles is contained in the core.

5. The dosage form according to claim 1 , wherein at least 90% by weight of the total amount of the active pharmaceutical ingredient in the core-shell particles is contained in the active pharmaceutical layer.

6. The dosage form according to claim 1 , wherein the dosage form further comprises a second type of core-shell particles that do not contain an active pharmaceutical layer.

7. The dosage form according to claim 6 , wherein the second type of core-shell particle comprises:
a core comprising a gelling polymer; and
at least one layer surrounding the core, the at least one layer comprising a pH-sensitive film comprising a pH-sensitive polymer that is insoluble in an aqueous environment with pH greater than 5.

8. The dosage form according to claim 1 , wherein the gelling polymer in the core 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.

9. The dosage form according to claim 2 , wherein the gelling polymer in the matrix comprises a carbomer polymer.

10. The dosage form according to claim 9 , wherein the gelling polymer in the matrix is present in an amount from 0.5 to 15 weight percent based on the total weight of the dosage form.

11. The dosage form according to claim 1 , wherein the pH-sensitive polymer is a copolymer of dimethyl aminoethyl methacrylate, butyl methacrylate, and methyl methacrylate monomers.

12. The dosage form according to claim 1 , wherein the supratherapeutic dose is five or more units of said dosage form.

13. 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.

14. The dosage form according to claim 13 , wherein the fatty alcohol is selected from glycerol behenate, glycerol palmitostearate, glycerol monostearate, and stearoyl macroglycerides.

15. 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 .

16. The method according to claim 15 , 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.

17. The method according to claim 15 , wherein the dosage form reduces the risk of abuse of the active pharmaceutical ingredient by nasal insufflation.

18. The method according to claim 15 , wherein the dosage form reduces the risk of abuse of the active pharmaceutical ingredient by injection.

19. A method for treating a subject having depression, comprising administering to the subject a dosage form according to claim 1 .

Assignees

• Clexio Biosciences Ltd

Inventors

• Haswani Dinesh K
• Moe Derek V
• O'Neill Victoria A
• Seburg Randal A
• Vega Zepeda Manuel A

Classifications

• A61K9/2886 Primary

  having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer (of the type active core-drug layer-inactive layer A61K9/209) · CPC title

• A61K47/59

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes · CPC title

• A61K47/61

  the organic macromolecular compound being a polysaccharide or a derivative thereof · CPC title

• A61K31/5513

  1,4-Benzodiazepines, e.g. diazepam {or clozapine} · CPC title

• A61K9/2009

  Inorganic compounds · CPC title