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 oral tablet comprising:
i. two types of core shell particles, each type comprising a core, the core comprising a first gelling polymer, wherein:
a. the first type of core-shell particles comprises an amount of an active pharmaceutical ingredient (API) in a first layer surrounding the core, wherein said API is selected from ketamine, esketamine, and pharmaceutically acceptable salts thereof and a pH sensitive polymer that is soluble in an aqueous environment at a pH below 5 and that at least partially surrounds the first layer; and
b. the second type of core-shell particles is without an API-containing layer;
and
ii. a matrix comprising a pH adjuster and a second gelling polymer,
wherein the immediate release provides for an immediate release profile having not less than 90% of API released in 60 minutes, wherein the release profile is evaluated by dissolution of the tablet in 300 mL of 0.1N HC1 media using USP II apparatus at 50 RPM paddle speed and 37° C.
2. The tablet according to claim 1 , wherein the first and second gelling polymers are independently selected from a natural starch, a synthetic starch, a natural cellulose, a synthetic cellulose, an acrylate, a polyalkylene oxide, a carbomer and combinations thereof.
3. The tablet according to claim 1 , wherein the first and second gelling polymers are independently selected from polyethylene oxide, polyvinyl alcohol, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethylmethylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, polyacrylic acid and polyvinyl carboxy polymers, carbomer polymers and combinations thereof.
4. The tablet according to claim 3 , wherein the first gelling polymer is hydroxypropyl methyl cellulose (HPMC).
5. The tablet according to claim 3 , wherein the second gelling polymer is a carbomer.
6. The tablet according to claim 1 , wherein the total amount of the first and second gelling polymers is about 0.7 to about 20 weight percent gelling polymer based on total weight of the dosage form.
7. The tablet according to claim 6 , wherein the total amount of the first and second gelling polymers is about 2 to about 15 weight percent gelling polymer based on total weight of the dosage form.
8. The tablet according to claim 1 , wherein the second gelling polymer is present in an amount from 0.5 to 15 weight percent based on the total weight of the dosage form.
9. The tablet according to claim 1 , wherein the pH adjuster is in an amount of about 1 to about 5 weight percent based on the total weight of the dosage form.
10. The tablet according to claim 9 , wherein the pH adjuster is in an amount of from about 2 to about 4 weight percent based on the total weight of the dosage form.
11. The tablet according to claim 5 , wherein the pH adjuster is present in an amount of about 1 to about 10 millimoles of the pH adjuster per gram of the carbomer polymer that is present in the dosage form.
12. The tablet according to claim 1 comprising esketamine, wherein the esketamine is present in a total amount of about 1mg to 400mg in the tablet.
13. The tablet according to claim 12 , wherein the esketamine is present in a total amount of about 1mg to about 100mg.
14. The tablet according to claim 12 , wherein the esketamine is present in a total amount of about 1mg to about 56mg.
15. The tablet according to claim 12 , wherein the esketamine is present in a total amount of about 1mg to about 28mg.
16. The tablet according to claim 1 , wherein the second type of core-shell particles comprise a pH sensitive polymer at least partially coating the core.
17. The tablet according to claim 1 , wherein the API is esketamine, the first gelling polymer is HPMC, and the second gelling polymer is a carbomer.
18. The tablet according to claim 1 , wherein said tablet confers abuse deterrence, and wherein the abuse deterrence comprises reducing the risk of one or more types of abuse selected from:
a) abuse by injection,
b) abuse by nasal insufflation, and
c) abuse by consumption of a supratherapeutic dose; or
d) combinations of the above.
19. An immediate release oral tablet comprising:
a first type and a second type of core shell particles, both types comprising
a core, the core comprising a first gelling polymer; and,
at least one layer comprising a pH-sensitive polymer that is soluble in an aqueous environment at a pH below 5;
wherein
a. the first type of core-shell particles comprises an active pharmaceutical ingredient (API) in a layer surrounding the core, wherein the layer surrounding the core is at least partially surrounded by said at least one layer comprising a pH sensitive polymer, said active pharmaceutical ingredient (API) selected from ketamine, esketamine and pharmaceutically acceptable salts thereof; and
b. the second type of core-shell particles does not comprise an API,
wherein the immediate release provides for an immediate release profile having not less than 90% of API released in 60 minutes, wherein the release profile is evaluated by dissolution of the tablet in 300 mL of 0.1N HC1 media using USP II apparatus at 50 RPM paddle speed and 37° C.
20. The tablet according to claim 19 , wherein the API is esketamine.
21. A method of treating a subject in need thereof comprising orally administering to the subject the tablet according to claim 1 .
22. A method of treating a subject in need thereof comprising orally administering to the subject the tablet according to claim 17 .
23. A method of treating a subject in need thereof comprising orally administering to the subject the tablet according to claim 20 .