Tamper resistant dosage forms

• US 8,808,741 B2
• Filed: 09/27/2013
• Issued: 08/19/2014
• 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 Pharma L.P.
• Inventors: McKenna, William H., Mannion, Richard O., O'Donnell, Edward P., Huang, Haiyong H.
• Primary Examiner(s): Arnold, Ernst V
• Assistant Examiner(s): Akhoon, Kauser M
• Application Number:
  US14/040,535
• Publication Number:
  US 20140031381A1
• Time in Patent Office: 326 Days
• Field of Search: None
• US Class Current: 424/472
• 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 method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet comprising an extended release matrix comprising a composition, wherein said tablet comprises:

(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000, and

(2) oxycodone or a pharmaceutically acceptable salt, and

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

(a) combining at least (1) and (2) to form a blend;

(b) shaping said blend to form a shaped tablet; and

(c) convection curing said shaped tablet by subjecting the shaped tablet to a temperature from about 60 to about 90°

C. for a time of from about 15 minutes to about 10 hours, wherein said

wherein said convection cured shaped tablet comprises;

(i) 5, 7.5, 10, 15, 20, or 30 mg of said oxycodone or pharmaceutically acceptable salt and at least 79% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000;

(ii) 40 mg of said oxycodone or pharmaceutically acceptable salt and at least 72% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000;

(iii) 60 mg of said oxycodone or pharmaceutically acceptable salt and at least 57% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000;

or

(iv) 80 mg of said oxycodone or pharmaceutically acceptable salt and at least 54% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000.

2. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 1, wherein said oxycodone or pharmaceutically acceptable salt is oxycodone hydrochloride.

3. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 1, wherein said time in said convection curing step is 30 minutes to 90 minutes.

4. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 1, wherein said temperature in said convection curing step is from 62 to 90°

C.

5. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 1, wherein said shaped tablet is coated before or after said convection curing step.

20. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 1, wherein said convection cured shaped tablet comprises 5, 7.5, 10, 15, 20, or 30 mg of said oxycodone or pharmaceutically acceptable salt and at least 79% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000.

21. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 1, wherein said convection cured shaped tablet comprises 40 mg of said oxycodone or pharmaceutically acceptable salt and at least 72% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000.

22. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 1, wherein said convection cured shaped tablet comprises 60 mg of said oxycodone or pharmaceutically acceptable salt and at least 57% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000.

23. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 1, wherein said convection cured shaped tablet comprises 80 mg of said oxycodone or pharmaceutically acceptable salt and at least 54% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000.

6. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet comprising an extended release matrix comprising a composition, wherein said tablet comprises:

(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000, and

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

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

(a) combining at least (1) and (2) to form a blend;

(b) shaping said blend to form a shaped tablet; and

(c) convection curing said shaped tablet by subjecting the shaped tablet to a temperature from about 60 to about 90°

C. for a time of from about 15 minutes to about 10 hours, wherein said polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000, in said blend is in an amount of at least 79% by weight, based upon the total weight of said composition.

7. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 6, wherein, said temperature in said convection curing step is from 62 to 90°

C.

8. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 6, wherein said shaped tablet is coated before or after said convection curing step.

9. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 6, wherein said opioid analgesic or pharmaceutically acceptable salt is selected form the group consisting of oxycodone, hydrocodone, hydromorphone, oxymorphone, morphine, or pharmaceutically acceptable salts of any of the foregoing.

10. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 9, wherein said opioid analgesic or pharmaceutically acceptable salt comprises oxycodone hydrochloride.

11. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 6, wherein said opioid analgesic or pharmaceutically acceptable salt comprises hydrocodone or a pharmaceutically acceptable salt thereof.

12. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 6, wherein said opioid analgesic or pharmaceutically acceptable salt comprises hydromorphone or a pharmaceutically acceptable salt thereof.

13. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 12, wherein said hydromorphone or a pharmaceutically acceptable salt thereof comprises hydromorphone hydrochloride.

14. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 6, wherein said opioid analgesic or pharmaceutically acceptable salt comprises oxymorphone or a pharmaceutically acceptable salt thereof.

15. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 14, wherein said oxymorphone or a pharmaceutically acceptable salt thereof comprises oxymorphone hydrochloride.

16. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 6, wherein said opioid analgesic or pharmaceutically acceptable salt comprises morphine or a pharmaceutically acceptable salt thereof.

17. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet comprising an extended release matrix comprising a composition, wherein said tablet comprises:

(1) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000, and

(2) oxycodone hydrochloride;

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

(a) combining at least (1) and (2) to form a blend;

(b) shaping said blend to form a shaped tablet; and

(c) convection curing said shaped tablet by subjecting the shaped tablet to a temperature from 62 to 90°

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

wherein said convection cured shaped tablet comprises;

(i) 5, 7.5, 10, 15, 20, or 30 mg of said oxycodone hydrochloride and at least 79% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000;

(ii) 40 mg of said oxycodone hydrochloride and at least 72% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000;

(iii) 60 mg of said oxycodone hydrochloride and at least 57% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000;

or

(iv) 80 mg of said oxycodone hydrochloride and at least 54% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000.

18. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 17, wherein said time in said convection curing step is 30 minutes to 90 minutes.

19. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 18, wherein said shaped tablet is coated before or after said convection curing step.

24. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 17, wherein said convection cured shaped tablet comprises 5, 7.5, 10, 15, 20, or 30 mg of said oxycodone hydrochloride and at least 79% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000.

25. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 17, wherein said convection cured shaped tablet comprises 40 mg of said oxycodone hydrochloride and at least 72% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000.

26. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 17, wherein said convection cured shaped tablet comprises 60 mg of said oxycodone hydrochloride salt and at least 57% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000.

27. A method of treating pain comprising administering to a patient in need thereof a convection cured shaped tablet as defined in claim 17, wherein said convection cured shaped tablet comprises 80 mg of said oxycodone hydrochloride and at least 54% by weight, based upon the total weight of said composition, of said at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of 4,000,000.