Abuse-proofed dosage form

• US 10,369,109 B2
• Filed: 07/11/2018
• Issued: 08/06/2019
• Est. Priority Date: 06/17/2002
• Status: Expired due to Term

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Bartholomaeus, Johannes, Kugelmann, Heinrich
• Primary Examiner(s): Worsham, Jessica
• Application Number:
  US16/032,533
• Publication Number:
  US 20180318223A1
• Time in Patent Office: 391 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine

Abstract

A solid administration form, protected from parenteral abuse and containing at least one viscosity-increasing agent in addition to one or more active substances that have parenteral abuse potential. The agent forms, when a necessary minimum amount of an aqueous liquid is added, on the basis of an extract obtained from the administration form, a preferably injectable gel that remains visually distinct when introduced into another quantity of an aqueous liquid.

Claims

1. A tablet for oral administration with reduced potential for parenteral abuse, said tablet comprising:

(a) one or more active ingredients having potential for abuse selected from the group consisting of hydrocodone, morphine, oxycodone, tramadol, and pharmaceutically acceptable salts and solvates thereof; and

(b) at least one viscosity-increasing agent in a quantity such that an aqueous extract of a total content of the tablet when comminuted and combined with 10 ml of water at 25°

C. forms a gel that can be drawn up into and injected back out of a hypodermic needle having a diameter of 0.9 mm, into a further quantity of water, wherein threads of the gel injected from said needle remain visible to the naked eye in said further quantity of water at 37°

C.

2. The tablet according to claim 1, wherein the active ingredient is oxycodone or a salt or solvate thereof.

3. The tablet according to claim 1, wherein the active ingredient is hydrocodone or a salt or solvate thereof.

4. The tablet according to claim 1, wherein the active ingredient is morphine or a salt or solvate thereof.

5. The tablet according to claim 1, wherein the one or more viscosity-increasing agents are selected from the group consisting of microcrystalline cellulose with 11 wt. % carboxymethylcellulose sodium, carboxymethylcellulose sodium, polyacrylic acid, locust bean flour, citrus pectin, waxy maize starch, sodium alginate, guar flour, iota-carrageenan, karaya gum, gellan gum, galactomannan, tara stone flour, propylene glycol alginate, apple pectin, lemon peel pectin, sodium hyaluronate, tragacanth, tara gum, fermented polysaccharide welan gum and xanthan gum.

6. The tablet according to claim 1, comprising at least one active ingredient in controlled release form.

7. The tablet according to claim 1, comprising a coating resistant to gastric juices.

8. The tablet according to claim 1, in multiparticulate form, wherein said multiparticulate form is in the form of microtablets, microcapsules, micropellets, granules, spheroids, beads or pellets, packaged in capsules or press-molded into tablets.

9. The tablet according to claim 1, wherein said threads remain visible to the naked eye in said further quantity of water for at least one minute.

10. The tablet according to claim 1, wherein said threads remain visible to the naked eye in said further quantity of water for at least ten minutes.

11. The tablet according to claim 1, which further comprises microcrystalline cellulose.

12. The tablet according to claim 1, which further comprises hydroxypropylmethylcellulose.

13. A solid dosage form for oral administration with reduced potential for parenteral abuse, said dosage form comprising:

(a) one or more active ingredients having potential for abuse selected from the group consisting of hydrocodone, morphine, oxycodone, tramadol, and pharmaceutically acceptable salts and solvates thereof; and

(b) one or more viscosity-increasing components, in a total quantity, for all said components combined, that is equal to or greater than 5 mg per dosage form, that quantity being selected such that an aqueous extract of a total content of the dosage form, when comminuted and combined with 10 ml of water at 25°

C., forms a gel that is capable of being drawn into and then expelled from a hypodermic needle having a diameter of 0.9 mm, wherein threads of said gel, formed upon exit from said needle into a further quantity of water at 37°

C., remain visible to the naked eye.

14. The dosage form according to claim 13, wherein the active ingredient is oxycodone or a salt or solvate thereof.

15. The dosage form according to claim 13, wherein the active ingredient is hydrocodone or a salt or solvate thereof.

16. The dosage form according to claim 13, wherein the active ingredient is morphine or a salt or solvate thereof.

17. The dosage form according to claim 13, wherein said threads remain visible to the naked eye in said further quantity of water for at least one minute.

18. The dosage form according to claim 13, wherein said threads remain visible to the naked eye in said further quantity of water for at least ten minutes.

19. The dosage form according to claim 13, comprising at least one active ingredient in controlled release form.

20. The dosage form according to claim 13, which further comprises microcrystalline cellulose.

21. The dosage form according to claim 13, which further comprises hydroxypropylmethylcellulose.

22. A tablet for oral administration with reduced potential for parenteral abuse, said tablet comprising:

(a) one or more active ingredients with potential for abuse selected from the group consisting of hydrocodone, morphine, oxycodone, tramadol and pharmaceutically acceptable salts and/or solvates thereof; and

(b) one or more viscosity-increasing agents;

wherein the tablet when its total content is comminuted and combined with 10 ml of water at 25°

C. forms an injectable gel that can be drawn up into and injected back out of a syringe having a diameter of 0.9 mm, but wherein the injectable gel cannot be safely injected from said syringe into a blood vessel of an abuser because the presence of the injectable gel in the abuser'"'"'s blood vessels would obstruct one or more of said abuser'"'"'s blood vessels.

23. The tablet according to claim 22, wherein the active ingredient is oxycodone or a salt or solvate thereof.

24. The tablet according to claim 22, wherein the active ingredient is hydrocodone or a salt or solvate thereof.

25. The tablet according to claim 22, wherein the active ingredient is morphine or a salt or solvate thereof.

26. The tablet according to claim 22, which further comprises microcrystalline cellulose.

27. The tablet according to claim 22, which further comprises hydroxypropylmethylcellulose.

28. The tablet according to claim 22, comprising at least one active ingredient in controlled release form.