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 oral immediate release abuse deterrent dosage form comprising:
core-shell particles comprising
a core that includes a gelling polymer and a wax, wherein the core does not include a sugar sphere or an active pharmaceutical ingredient;
an active pharmaceutical layer surrounding the core, the active pharmaceutical layer comprising an active pharmaceutical ingredient, wherein the active pharmaceutical ingredient is a dissociative anesthetic agent that is selected from the group consisting of ketamine, esketamine, and an isotopically-enriched compound thereof; and
at least one layer surrounding the active pharmaceutical layer, the at least one layer comprising 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.
2. The dosage form according to claim 1 , wherein said dosage form further comprises a matrix comprising a disintegrant and a gelling polymer.
3. The dosage form according to claim 1 , wherein the dosage is in a compressed tablet form.
4. The dosage form according to claim 1 , wherein at least 90 percent of the total amount of the active pharmaceutical ingredient in the core shell particles is contained in the active pharmaceutical layer.
5. 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.
6. The dosage form according to claim 5 , 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.
7. 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.
8. The dosage form according to claim 2 , wherein the gelling polymer in the matrix is a carbomer polymer.
9. The dosage form according to claim 2 , wherein, 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.
10. 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.
11. The dosage form according to claim 1 , wherein the supratherapeutic dose is five or more tablets.
12. A method of reducing the potential for abuse by a human of an active pharmaceutical ingredient by simultaneous oral ingestion of multiple dosage units of said active pharmaceutical ingredient, the method comprising providing an oral immediate release abuse deterrent dosage form according to claim 1 .
13. The method according to claim 12 , wherein the active pharmaceutical ingredient is selected from the group consisting of esketamine and an isotopically enriched compound thereof.
14. The method according to claim 12 , wherein the gelling polymer in the core is selected from the group consisting of a synthetic cellulose, an acrylate, a polyalkylene oxide, a carbomer and combinations thereof and,
the dosage form further comprises a matrix comprising a disintegrant and a gelling polymer.
15. The method according to claim 14 , wherein the gelling polymer in the matrix is selected from the group consisting of a synthetic cellulose, a polyalkylene oxide, a carbomer, and combinations thereof.
16. The method according to claim 14 , wherein at least 90 percent of the total amount of the active pharmaceutical ingredient in the core shell particles is contained in the active pharmaceutical layer.
17. The method according to claim 12 , wherein the dosage form further comprises a second type of core-shell particles that do not contain an active pharmaceutical layer, the second type of core-shell particles comprising:
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 pH-sensitive polymer that is insoluble at a pH greater than 5.
18. The method according to claim 14 , wherein the gelling polymer in the matrix is a carbomer polymer.
19. The method according to claim 14 , 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.
20. The method according to claim 12 , wherein the pH-sensitive polymer is a copolymer of dimethyl aminoethyl methacrylate, butyl methacrylate, and methyl methacrylate monomers.
21. The method according to claim 12 , wherein the dosage form reduces the risk of an overdose of the dissociative anesthetic by simultaneous oral ingestion of multiple units of the oral dosage form.
22. The dosage form according to claim 1 , wherein the wax 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.
23. The dosage form according to claim 22 , wherein the fatty alcohol is selected from glycerol behenate, glycerol palmitostearate, glycerol monostearate, and stearoyl macroglycerides.
24. The dosage form according to claim 2 , wherein said matrix further comprises sodium bicarbonate.
25. The dosage form according to claim 24 , wherein the sodium bicarbonate is present in an amount of about 1-5 wt % based on the total weight of the dosage form.
26. The dosage form according to claim 24 , wherein the sodium bicarbonate is present in an amount of about 5-20 wt % based on the total weight of the dosage form.
27. The method according to claim 12 , wherein said dosage form further comprises a matrix comprising a carbomer polymer and sodium bicarbonate.
28. The method according to claim 27 , wherein the sodium bicarbonate is present in an amount of about 1-5 wt % based on the total weight of the dosage form.
29. The method according to claim 27 , wherein the sodium bicarbonate is present in an amount of about 5-20 wt % based on the total weight of the dosage form.
30. The dosage form according to claim 1 , wherein the active pharmaceutical ingredient is selected from the group consisting of esketamine and an isotopically enriched compound thereof.