Pharmaceutical formulation containing gelling agent

• US 20030068375A1
• Filed: 08/06/2002
• Published: 04/10/2003
• Est. Priority Date: 08/06/2001
• Status: Abandoned Application

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Wright, Curtis, Oshlack, Benjamin, Breder, Christopher
• Application Number:
  US10/214,412
• Publication Number:
  US 20030068375A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61J 3/10 into the form of compressed tablets tablet presses B30B11/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/48 Ergoline derivatives, e.g. lysergic acid, ergotamine
• 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 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/08 containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
• 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 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• 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 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 8/731 : Cellulose; Quaternized cellulose derivatives
• 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 9/006 : Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/0095 : Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/06 : Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/08 : Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/1635 : obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• 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 9/1652 : Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/19 : lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/20 : Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2009 : Inorganic compounds
• CPC Class Codes: A61K 9/2013 : Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 : 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 9/205 : Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 : Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2095 : 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 9/2806 : Coating materials
• CPC Class Codes: A61K 9/2813 : Inorganic compounds
• CPC Class Codes: A61K 9/284 : obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2846 : Poly(meth)acrylates
• 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: A61K 9/48 : Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4808 : characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/4833 : Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61K 9/485 : Inorganic compounds
• CPC Class Codes: A61K 9/4858 : Organic compounds
• CPC Class Codes: A61K 9/4866 : Organic macromolecular compounds
• CPC Class Codes: A61K 9/4875 : Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/4858
• CPC Class Codes: A61K 9/4891 : Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61K 9/5047 : Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 : with drug-free core
• CPC Class Codes: A61K 9/5089 : Processes
• CPC Class Codes: A61K 9/70 : Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/36 : Opioid-abuse

Abstract

Disclosed in certain embodiments is a controlled release oral dosage form comprising a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients; the dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid; the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.

Claims

1. A controlled release oral dosage form comprising:

a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients;

said dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid;

said dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.

2. The controlled release oral dosage form of claim 1, wherein said excipient comprises a controlled release material.

3. The controlled release oral dosage form of claim 1, wherein said gelling agent comprises a controlled release material.

4. The controlled release oral dosage form of claim 1, wherein said drug is an opioid analgesic selected from the group consisting of levorphanol, meperidine, dihydrocodeine, dihydromorphine, oxymorphone, pharmaceutically acceptable salts thereof, and mixtures thereof.

5. The controlled release oral dosage form of claim 1, wherein said drug is an opioid analgesic.

6. The controlled release oral dosage form of claim 5, wherein said opioid analgesic is morphine or a pharmaceutically acceptable salt thereof.

7. The controlled release oral dosage form of claim 5, wherein said opioid analgesic is hydromorphone or a pharmaceutically acceptable salt thereof.

8. The controlled release oral dosage form of claim 5, wherein said opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof.

9. The controlled release oral dosage form of claim 5, wherein said opioid analgesic is oxycodone or a pharmaceutically acceptable salt thereof.

10. The controlled release oral dosage form of claim 5, wherein said opioid analgesic is codeine or a pharmaceutically acceptable salt thereof.

11. The oral dosage form of claim 1, wherein said drug is selected from the group consisting of a tranquilizer, a CNS depressant, a CNS stimulant (e.g., methylphenidate or a pharmaceutically acceptable salt thereof), a sedative hypnotic, and combinations thereof.

12. The controlled release oral dosage form of claim 1, wherein said ratio of said gelling agent to said drug is from about 1:

40 to about 40;

1.

13. The controlled release oral dosage form of claim 1, wherein said ratio of said gelling agent to said drug is from about 1:

1 to about 30;

1.

14. The controlled release oral dosage form of claim 1, wherein said ratio of said gelling agent to said drug is from about 2:

1 to about 10;

1.

15. The controlled release oral dosage form of claim 1, wherein said gelling agent is selected from the group consisting of sugars, sugar derived alcohols, cellulose derivatives, gums, surfactants, emulsifying agents, and mixtures thereof.

16. The controlled release oral dosage form of claim 1, wherein said gelling agent is selected from the group consisting of pectin, xanthan gum and combinations thereof.

17. The controlled release oral dosage form of claim 1, wherein said aqueous liquid is water.

18. The controlled release oral dosage form of claim 1, wherein said unsuitable viscosity is attained when about 1 to about 3 ml of aqueous liquid is mixed with the crushed dosage form.

19. The controlled release oral dosage form of claim 1, wherein the addition of from about 0.5 to about 10 ml of said aqueous liquid causes said solubilized mixture to have a viscosity of at least about 10 cP.

20. The controlled release oral dosage form of claim 1, wherein the addition of from about 0.5 to about 10 ml of said aqueous liquid causes said solubilized mixture to have a viscosity of at least about 60 cP.

21. The controlled release oral dosage form of claim 4, further comprising an additional drug selected from the group consisting of an NSAID, a COX-2 inhibitor, acetaminophen, aspirin, an NMDA receptor antanalgesic, a drug that blocks a major intracellular consequence of NMDA-receptor activation, an antitussive, an expectorant, a decongestant, an antihistamine and mixtures thereof.

22. A method of preventing abuse of an oral controlled release dosage form of a drug comprising:

preparing the dosage form with a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients;

said dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid;

said dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.

23. The method of claim 22, wherein said excipient comprises a controlled release material.

24. The method of claim 22, wherein said gelling agent comprises a controlled release material.

25. The method of claim 22, wherein the addition of from about 0.5 to about 10 ml of said aqueous liquid causes said solubilized mixture to have a viscosity of at least about 10 cP.

26. The method of claim 22, wherein the addition of from about 0.5 to about 10 ml of said aqueous liquid causes said solubilized mixture to have a viscosity of at least about 25 cP.

27. The method of claim 22, wherein the addition of from about 0.5 to about 10 ml of said aqueous liquid causes said solubilized mixture to have a viscosity of at least about 60 cP.

28. The method of claim 22, wherein said drug is an opioid analgesic selected from the group consisting of of morphine, hydromorphone, hydrocodone, oxycodone, codeine, levorphanol, meperidine, dihydrocodeine, dihydromorphine, oxymorphone, pharmaceutically acceptable salts thereof and mixtures thereof.

29. The method of claim 22, wherein said gelling agent is selected from the group consisting of sugars or sugar derived alcohols, cellulose derivatives, gums, surfactants, emulsifying agents, and mixtures thereof. comprises a controlled release material.

30. A controlled release oral dosage form comprising:

a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients;

said dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid and thereafter heated;

said dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.

31. A method of preventing abuse of an oral controlled release dosage form of a drug comprising:

preparing the dosage form with a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients;

said dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid and is thereafter heated;

said dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.

32. A method of preventing diversion of an oral controlled release dosage form of a drug comprising:

preparing the dosage form with a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients;

said dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid;

said dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.

33. The method of claim 32, wherein said excipient comprises a controlled release material.

34. The method of claim 32, wherein said gelling agent comprises a controlled release material.

35. The method of claim 32, wherein the addition of from about 0.5 to about 10 ml of said aqueous liquid causes said solubilized mixture to have a viscosity of at least about 10 cP.

36. The method of claim 32, wherein the addition of from about 0.5 to about 10 ml of said aqueous liquid causes said solubilized mixture to have a viscosity of at least about 25 cP.

37. The method of claim 32, wherein said drug is a opioid analgesic selected from the group consisting of morphine, hydromorphone, hydrocodone, oxycodone, codeine, levorphanol, meperidine, dihydrocodeine, dihydromorphine, oxymorphone, pharmaceutically acceptable salts thereof and mixtures thereof.

38. The method of claim 32, wherein said gelling agent is selected from the group consisting of sugars or sugar derived alcohols, cellulose derivatives, gums, surfactants, emulsifying agents, and mixtures thereof.

39. A method of treating pain comprising:

administering to a patient a therapeutically effective amount of an opioid analgesic together with pharmaceutically acceptable excipients such that the dosage form provides effective pain relief for at least about 12 hours when orally administered to a human patient;

said dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for injection to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid.

40. A controlled release oral dosage form of comprising:

a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients;

and a gelling agent in an effective amount to impart a viscosity unsuitable for nasal absorption of the drug upon administration to the nasal passages after tampering;

said dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.