Tamper resistant dosage forms

• US 10,076,499 B2
• Filed: 01/31/2018
• Issued: 09/18/2018
• Est. Priority Date: 08/25/2006
• Status: Active Grant

• Current Assignee: Purdue Pharmaceuticals L.P. (Purdue Pharma L.P.), Purdue Pharma L.P.
• Original Assignee: Purdue Pharmaceuticals L.P. (Purdue Pharma L.P.), Purdue Pharma L.P.
• Inventors: McKenna, William H., Mannion, Richard O., O'Donnell, Edward P., Huang, Haiyong H.
• Primary Examiner(s): Fubara, Blessing M
• Application Number:
  US15/885,413
• Publication Number:
  US 20180153815A1
• Time in Patent Office: 230 Days
• CPC Class Codes: A61J 3/005 Coating of tablets or the like coating of sweetmeats or confectionery A23G3/20; coating of granules in general B01J2/006
• CPC Class Codes: A61J 3/06 into the form of pills, lozenges or dragees
• CPC Class Codes: A61J 3/10 into the form of compressed tablets tablet presses B30B11/00
• 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 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• 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 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• 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: A61K 9/284 : obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2853 : obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/2866 : Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2893 : Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 : without antiinflammatory effect
• CPC Class Codes: B29B 7/02 : non-continuous, with mechanical mixing or kneading devices, i.e. batch type
• CPC Class Codes: B29B 7/88 : Adding charges , i.e. additives
• CPC Class Codes: B29C 2035/046 : dried air
• CPC Class Codes: B29C 2035/1658 : using gas
• CPC Class Codes: B29C 35/045 : using gas or flames
• CPC Class Codes: B29C 35/16 : Cooling cooling extruded material B29C48/911; cooling preforms for blow moulding B29C49/6427; cooling blown articles B29C49/66; cooling tyres during post cure inflation B29D30/0643
• CPC Class Codes: B29C 37/0025 : Applying surface layers, e.g. coatings, decorative layers, printed layers, to articles during shaping, e.g. in-mould printing moulding on preformed layers as inserts B29C70/68; applying fluent material to surfaces in general B05
• CPC Class Codes: B29C 43/003 : characterised by the choice of material
• CPC Class Codes: B29C 43/02 : of articles of definite length, i.e. discrete articles B29C35/0227 takes precedence
• CPC Class Codes: B29C 43/52 : Heating or cooling
• CPC Class Codes: B29C 71/00 : After-treatment of articles without altering their shape; Apparatus therefor B29C44/56, B29C73/00 take precedence; surface shaping B29C59/00 ; for joined or sealed parts B29C66/03; after-treatment specially adapted for vulcanising tyres B29D30/0633
• CPC Class Codes: B29C 71/009 : using gases without chemical reaction C08J7/12 takes precedence; in combination with blow-moulding B29C49/46; surface treatment using plasma B29C59/14, ionised gas B29C59/16
• CPC Class Codes: B29K 2071/02 : Polyalkylene oxides, e.g. PEO, i.e. polyethylene oxide, or derivatives thereof
• CPC Class Codes: B29K 2105/0035 : Medical or pharmaceutical agents
• CPC Class Codes: B29K 2105/251 : Particles, powder or granules expandable particles B29K2105/046
• CPC Class Codes: B29K 2995/0088 : Molecular weight
• CPC Class Codes: B29L 2031/753 : Medical equipment; Accessories therefor bloodbags, medical bags B29L2031/7148; artificial eyes B29L2011/0008

Abstract

The present invention relates to pharmaceutical dosage forms, for example to a tamper resistant dosage form including an opioid analgesic, and processes of manufacture, uses, and methods of treatment thereof.

Claims

1. A cured shaped extended release tablet comprising:

(1) at least one high molecular weight polyethylene oxide having, based on rheological measurements, an approximate molecular weight selected from 4,000,000 and 7,000,000; and

(2) oxycodone or a pharmaceutically acceptable salt;

wherein said tablet is prepared by a process comprising the steps of;

(a) forming a tablet-shaped pharmaceutical preparation comprising said oxycodone or pharmaceutically acceptable salt thereof and said high molecular weight polyethylene oxide;

(b) curing said tablet-shaped pharmaceutical preparation by subjecting said preparation to a temperature from about 60°

C. to about 90°

C. for a time of from about 15 minutes to about 10 hours; and

(c) optionally applying at least one coating to said tablet-shaped pharmaceutical preparation, before, during or after curing;

wherein said tablet comprises;

(i) 5, 7.5, 10, 15, 20, or 30 mg of said oxycodone or pharmaceutically acceptable salt thereof, and at least 79% by weight of said high molecular weight polyethylene oxide;

(ii) 40 mg of said oxycodone or pharmaceutically acceptable salt thereof, and at least 72% by weight of said high molecular weight polyethylene oxide;

(iii) 60 mg of said oxycodone or pharmaceutically acceptable salt thereof, and at least 57% by weight of said high molecular weight polyethylene oxide;

or

(iv) 80 mg of said oxycodone or pharmaceutically acceptable salt thereof, and at least 54% by weight of said high molecular weight polyethylene oxide; and

wherein percent by weight is based upon the total weight of said tablet-shaped pharmaceutical preparation, not including the combined weight of said applied coatings.

2. A tablet as defined in claim 1, wherein said oxycodone or pharmaceutically acceptable salt thereof is oxycodone hydrochloride.

3. A tablet as defined in claim 1, wherein said time in said curing step is from about 30 minutes to about 90 minutes.

4. A tablet as defined in claim 1, wherein said temperature in said curing step is from about 62°

C. to about 90°

C.

5. A tablet as defined in claim 1, wherein at least one coating is applied to said tablet-shaped pharmaceutical preparation, before, during or after said curing step.

6. A tablet as defined in claim 1, wherein said tablet comprises 5, 7.5, 10, 15, 20, or 30 mg of said oxycodone or pharmaceutically acceptable salt thereof;

said high molecular weight polyethylene oxide has an approximate molecular weight of 4,000,000; and

the percent by weight of said high molecular weight polyethylene oxide is at least 79%.

7. A tablet as defined in claim 1, wherein said tablet comprises 40 mg of said oxycodone or pharmaceutically acceptable salt thereof;

said high molecular weight polyethylene oxide has an approximate molecular weight of 4,000,000; and

the percent by weight of said high molecular weight polyethylene oxide is at least 72%.

8. A tablet as defined in claim 1, wherein said tablet comprises 60 mg of said oxycodone or pharmaceutically acceptable salt thereof;

said high molecular weight polyethylene oxide has an approximate molecular weight of 4,000,000; and

the percent by weight of said high molecular weight polyethylene oxide is at least 57%.

9. A tablet as defined in claim 1, wherein said tablet comprises 80 mg of said oxycodone or pharmaceutically acceptable salt thereof;

said high molecular weight polyethylene oxide has an approximate molecular weight of 4,000,000; and

the percent by weight of said high molecular weight polyethylene oxide is at least 54%.

10. A tablet as defined in claim 1, wherein said curing comprises convection curing in a convection curing device.

11. A tablet as defined in claim 1, wherein said cured tablet-shaped pharmaceutical preparation has a density that is at least about 1% lower than the density of said preparation prior to curing.

12. A tablet as defined in claim 1, wherein said tablet-shaped pharmaceutical preparation is formed by direct compression.

13. A tablet as defined in claim 12, wherein said tablet comprises 5, 7.5, 10, 15, 20, or 30 mg of said oxycodone or pharmaceutically acceptable salt thereof;

said high molecular weight polyethylene oxide has an approximate molecular weight of 4,000,000; and

the percent by weight of said high molecular weight polyethylene oxide is at least 79%.

14. A tablet as defined in claim 12, wherein said tablet comprises 40 mg of said oxycodone or pharmaceutically acceptable salt thereof;

said high molecular weight polyethylene oxide has an approximate molecular weight of 4,000,000; and

the percent by weight of said high molecular weight polyethylene oxide is at least 72%.

15. A tablet as defined in claim 12, wherein said tablet comprises 60 mg of said oxycodone or pharmaceutically acceptable salt thereof;

said high molecular weight polyethylene oxide has an approximate molecular weight of 4,000,000; and

the percent by weight of said high molecular weight polyethylene oxide is at least 57%.

16. A tablet as defined in claim 12, wherein said tablet comprises 80 mg of said oxycodone or pharmaceutically acceptable salt thereof;

said high molecular weight polyethylene oxide has an approximate molecular weight of 4,000,000; and

the percent by weight of said high molecular weight polyethylene oxide is at least 54%.

17. A tablet as defined in claim 12, wherein said curing comprises curing in a convection curing device.

18. A tablet as defined in claim 12, wherein said cured tablet-shaped pharmaceutical preparation has a density that is at least about 1% lower than the density of said preparation prior to curing.

19. A tablet as defined in claim 12, wherein said cured tablet-shaped pharmaceutical preparation has a density that is at least about 2% lower than the density of said preparation prior to curing.

20. A cured shaped extended release tablet comprising:

(1) at least one high molecular weight polyethylene oxide having, based on rheological measurements, an approximate molecular weight selected from 4,000,000 and 7,000,000; and

(2) an opioid analgesic or a pharmaceutically acceptable salt thereof;

wherein said tablet is prepared by a process comprising the steps of;

(a) forming a tablet-shaped pharmaceutical preparation comprising said opioid or pharmaceutically acceptable salt thereof and said high molecular weight polyethylene oxide;

(b) curing said tablet-shaped pharmaceutical preparation by subjecting said preparation to a temperature from about 60°

C. to about 90°

C. for a time of from about 15 minutes to about 10 hours; and

(c) optionally applying at least one coating to said tablet-shaped pharmaceutical preparation, before, during or after curing;

wherein said high molecular weight polyethylene oxide is in an amount of at least 54%, by weight, based upon the total weight of said tablet-shaped pharmaceutical preparation, not including the combined weight of said applied coatings.

21. A tablet as defined in claim 20, wherein, said temperature in said curing step is from about 62°

C. to about 90°

C.

22. A tablet as defined in claim 20, wherein at least one coating is applied to said tablet-shaped pharmaceutical preparation, before, during or after said curing step.

23. A tablet as defined in claim 20, wherein the percent by weight of said high molecular weight polyethylene oxide is at least 80%, and said opioid analgesic or pharmaceutically acceptable salt comprises hydrocodone or a pharmaceutically acceptable salt thereof.

24. A tablet as defined in claim 20, wherein the percent by weight of said high molecular weight polyethylene oxide is at least 80%, and said opioid analgesic or pharmaceutically acceptable salt thereof comprises hydromorphone or a pharmaceutically acceptable salt thereof.

25. A tablet as defined in claim 24, wherein said hydromorphone or pharmaceutically acceptable salt thereof comprises hydromorphone hydrochloride.

26. A tablet as defined in claim 20, wherein the percent by weight of said high molecular weight polyethylene oxide is at least 80%, and said opioid analgesic or pharmaceutically acceptable salt comprises oxymorphone or a pharmaceutically acceptable salt thereof.

27. A tablet as defined in claim 26, wherein the percent by weight of said high molecular weight polyethylene oxide is at least 80%, and said oxymorphone or pharmaceutically acceptable salt thereof comprises oxymorphone hydrochloride.

28. A tablet as defined in claim 20, wherein the percent by weight of said high molecular weight polyethylene oxide is at least 80%, and said opioid analgesic or pharmaceutically acceptable salt comprises morphine or a pharmaceutically acceptable salt thereof.

29. A tablet as defined in claim 20, wherein said curing comprises convection curing in a convection curing device.

30. A tablet as defined in claim 20, wherein said cured tablet-shaped pharmaceutical preparation has a density that is at least about 1% lower than the density of said preparation prior to curing.