Abuse-deterrent pharmaceutical compositions for controlled release

• US 9,044,402 B2
• Filed: 04/10/2014
• Issued: 06/02/2015
• Est. Priority Date: 07/06/2012
• Status: Expired due to Fees

• Current Assignee: Egalet, Ltd. (Assertio Holdings, Inc.)
• Original Assignee: Egalet, Ltd. (Assertio Holdings, Inc.)
• Inventors: Tygesen, Peter Holm, Lindhardt, Karsten, Olsen, Martin Rex, Fischer, Gina Engslev, Overgard, Jan Martin, Boye, Georg, Skak, Nikolaj, Elhauge, Torben
• Primary Examiner(s): Yu, Misook
• Assistant Examiner(s): Akhoon, Kauser M
• Application Number:
  US14/249,965
• Publication Number:
  US 20140220126A1
• Time in Patent Office: 418 Days
• Field of Search: None
• US Class Current: 1/1
• 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 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine

Abstract

The present disclosure relates to pharmaceutical compositions that are abuse resistant and may also provide controlled release. The present disclosure also relates to the use of pharmaceutical compositions in the treatment of pain.

Claims

1. An abuse-deterrent tablet formulated for oral administration of an opioid, the tablet consisting of a tablet composition and, optionally, a cosmetic coat, wherein:

the tablet composition comprises;

about 1-30% w/w of the opioid; and

about 70-98% w/w of a polyethylene oxide (PEO) having an average molecular weight of from about 400,000 daltons to about 600,000 daltons; and

the cosmetic coat, when present, covers at least a portion of the tablet composition, and dissolves within 30 minutes after contact with an aqueous media,

wherein the tablet composition does not provide immediate release of the opioid even after the abuse-deterrent tablet is subjected to physical tampering selected from crushing, grinding, grating, cutting, or crisping, and

wherein the tablet composition exhibits a viscosity of at least 170 mPa·

s when measured by Viscosity Test #2, or a viscosity of at least 46 Pa·

s when measured by Viscosity Test #1.

2. The abuse deterrent tablet of claim 1, wherein the opioid is selected from the group consisting of buprenorphine, codeine, dextromoramide, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, morphine, pentazocine, oxycodeine, oxycodone, oxymorphone, norhydrocodone, noroxycodone, morphine-6-glucuronode, tramadol, tapentadol, dihydromorphine, and pharmaceutically acceptable salts thereof.

3. The abuse deterrent tablet of claim 1, wherein the opioid is selected from the group consisting of morphine and pharmaceutically acceptable salts thereof.

4. The abuse deterrent tablet of claim 1, wherein the tablet composition exhibits a release rate of opioid in ethanol that is equal to or lower than the release rate of opioid in water.

5. The abuse deterrent tablet of claim 1, wherein the tablet yields a non-snortable composition when subjected to physical tampering selected from crushing, hammering, grinding, grating, and cutting.

19. A method for treating an individual suffering from moderate to severe pain, the method comprising administering to the individual an abuse-deterrent tablet according to claim 1.

21. The abuse deterrent tablet of claim 1, wherein the average molecular weight of the PEO included in the tablet composition is about 400,000 daltons.

6. An abuse-deterrent tablet formulated for oral administration of an opioid, consisting of a tablet composition and, optionally, a cosmetic coat, wherein:

the tablet composition comprises;

about 1-30% w/w of the opioid; and

about 70-98% w/w of a polyethylene oxide (PEO) blend comprising two or more PEOs, wherein each of the two or more PEOs has a different average molecular weight and the average molecular weight of the blend of the two or more PEOs included in the tablet composition is from about 400,000 daltons to about 600,000 daltons; and

the cosmetic coat, when present, covers at least a portion of the tablet composition, and dissolves within 30 minutes after contact with an aqueous media,

wherein the tablet composition does not provide immediate release of the opioid even after the abuse-deterrent tablet is subjected to physical tampering selected from crushing, grinding, grating, cutting, or crisping, and

wherein the tablet composition exhibits a viscosity of at least 170 mPa·

s when measured by Viscosity Test #2, or a viscosity of at least 46 Pa·

s when measured by Viscosity Test #1.

7. The abuse deterrent tablet of claim 6, wherein the opioid is selected from the group consisting of buprenorphine, codeine, dextromoramide, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, morphine, pentazocine, oxycodeine, oxycodone, oxymorphone, norhydrocodone, noroxycodone, morphine-6-glucuronode, tramadol, tapentadol, dihydromorphine, and pharmaceutically acceptable salts thereof.

8. The abuse deterrent tablet of claim 6, wherein the opioid is selected from the group consisting of morphine and pharmaceutically acceptable salts thereof.

9. The abuse deterrent tablet of claim 6, wherein the PEO blend includes a first PEO having an average molecular weight of about 200,000 daltons and a second PEO having an average molecular weight of about 600,000 daltons, wherein the average molecular weight of the PEO blend included in the tablet composition is about 400,000 daltons.

10. The abuse deterrent tablet of claim 6, wherein the tablet composition exhibits a release rate of opioid in ethanol that is equal to or lower than the release rate of opioid in water.

11. The abuse deterrent tablet of claim 6, wherein the tablet yields a non-snortable composition when subjected to physical tampering selected from crushing, hammering, grinding, grating, and cutting.

20. A method for treating an individual suffering from moderate to severe pain, the method comprising administering to the individual an abuse-deterrent tablet according to claim 6.

22. The abuse deterrent tablet of claim 6, wherein the average molecular weight of the PEO blend included in the tablet composition is about 400,000 daltons.

12. An abuse-deterrent tablet formulated for oral administration of an opioid, consisting of a tablet composition and, optionally, a cosmetic coat, wherein:

the tablet composition comprises;

about 1-30% w/w of the opioid;

about 70-98% w/w of a polyethylene oxide (PEO) selected from a single PEO having an average molecular weight of from about 400,000 daltons to about 600,000 daltons and a PEO blend comprising two or more PEOs, wherein each of the two or more PEOs has a different average molecular weight and the average molecular weight of the blend of the two or more PEOs included in the tablet composition is from about 400,000 daltons to about 600,000 daltons; and

at least 1% w/w of a plasticizer; and

the cosmetic coat, when present, covers at least a portion of the tablet composition, and dissolves within 30 minutes after contact with an aqueous media,

wherein the tablet composition does not provide immediate release of the opioid even after the abuse-deterrent tablet is subjected to physical tampering selected from crushing, grinding, grating, cutting, or crisping, and

wherein the tablet composition exhibits a viscosity of at least 170 mPa·

s when measured by Viscosity Test #2 or a viscosity of at least 46 Pa·

s when measured by Viscosity Test #1.

13. The abuse deterrent tablet of claim 12, wherein the opioid is selected from the group consisting of buprenorphine, codeine, dextromoramide, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, morphine, pentazocine, oxycodeine, oxycodone, oxymorphone, norhydrocodone, noroxycodone, morphine-6-glucuronode, tramadol, tapentadol, dihydromorphine, and pharmaceutically acceptable salts thereof.

14. The abuse deterrent tablet of claim 12, wherein the opioid is selected from the group consisting of morphine and pharmaceutically acceptable salts thereof.

15. The abuse deterrent tablet of claim 12, wherein the tablet composition exhibits a release rate of opioid in ethanol that is equal to or lower than the release rate of opioid in water.

16. The abuse deterrent tablet of claim 12, wherein the plasticizer is selected from the group consisting of poloxamers having an average molecular weight from about 3,000 to about 30,000 daltons.

17. The abuse deterrent tablet of claim 12, wherein the tablet yields a non-snortable composition when subjected to physical tampering selected from crushing, hammering, grinding, grating, and cutting.

18. A method for treating an individual suffering from moderate to severe pain, the method comprising administering to the individual an abuse-deterrent tablet according to claim 12.

23. The abuse deterrent tablet of claim 12, wherein the average molecular weight of the PEO or PEO blend included in the tablet composition is about 400,000 daltons.