Pharmaceutical Formulation Containing Gelling Agent

• US 20150182628A1
• Filed: 03/16/2015
• Published: 07/02/2015
• Est. Priority Date: 08/06/2001
• Status: Active Grant

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharmaceuticals L.P. (Purdue Pharma L.P.), The PF Laboratories, Inc. (Purdue Pharma L.P.)
• Inventors: Wright, Curtis, Oshlack, Benjamin, Breder, Christopher
• Granted Patent: US 9,387,173 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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

1-40. -40. (canceled)

41. A controlled release oral solid dosage form comprising:

(i) controlled release particles comprising a plurality of inert beads coated with hydrocodone bitartrate, the hydrocodone bitartrate coated beads overcoated with an ammonio methacrylate copolymer;

(ii) immediate release particles comprising a plurality of inert beads coated with hydrocodone bitartrate and hydroxypropylmethylcellulose;

(iii) a gelling agent comprising polyethylene oxide;

the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient, and having a viscosity unsuitable for parenteral administration when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

42. The controlled release oral solid dosage form of claim 41, wherein the gelling agent is incorporated in the controlled release particles.

43. The controlled release oral solid dosage form of claim 41, wherein the gelling agent is separate from the controlled release particles and the immediate release particles.

44. The controlled release oral solid dosage form of claim 43, wherein the gelling agent is in the form of particles.

45. The controlled release oral solid dosage form of claim 44, wherein the gelling agent particles comprise the gelling agent coated onto a plurality of inert beads.

46. The controlled release oral solid dosage form of claim 45, wherein the gelling agent particles further comprise polyvinylpyrrolidone.

47. The controlled release oral solid dosage form of claim 44, wherein the controlled release particles, the immediate release particles and the gelling agent particles are contained in a pharmaceutically acceptable capsule.

48. The controlled release oral solid dosage form of claim 47, wherein the gelling agent particles and the controlled release particles have similar appearance.

49. The controlled release oral solid dosage form of claim 41, comprising from about 75 ng to about 750 mg hydrocodone bitartrate.

50. The controlled release oral solid dosage form of claim 41, comprising from about 2 mg to about 50 mg hydrocodone bitartrate.

51. The controlled release oral solid dosage form of claim 41, wherein the controlled release particles further comprise a plasticizer.

52. The controlled release oral solid dosage form of claim 41, wherein the controlled release particles further comprise talc.

53. The controlled release oral solid dosage form of claim 41, wherein the controlled release particles have a diameter from about 0.5 mm to about 2.5 mm.

54. The controlled release oral solid dosage form of claim 41, wherein the gelling agent is in an effective amount to impart a viscosity of at least about 10 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

55. The controlled release oral solid dosage form of claim 41, wherein the gelling agent is in an effective amount to impart a viscosity of at least about 60 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

56. The controlled release oral solid dosage form of claim 41, wherein the gelling agent is in an effective amount to impart a viscosity of at least about 120 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

57. The controlled release oral solid dosage form of claim 41, wherein the gelling agent is in an effective amount to impart a viscosity of at least about 375 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

58. The controlled release oral solid dosage form of claim 41, wherein the gelling agent is in an effective amount to impart a viscosity of at least about 2,000 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

59. The controlled release oral solid dosage form of claim 41, wherein the gelling agent is in an effective amount to impart a viscosity from about 120 cP to about 5,000 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

60. A controlled release oral solid dosage form comprising a capsule containing:

(i) controlled release particles comprising a plurality of inert beads coated with hydrocodone bitartrate, the hydrocodone bitartrate coated beads overcoated with an ammonio methacrylate copolymer;

(ii) immediate release particles comprising a plurality of inert beads coated with hydrocodone bitartrate and hydroxypropylmethylcellulose;

(iii) a gelling agent comprising polyethylene oxide;

the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient, and having a viscosity of at least 120 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

61. The controlled release oral solid dosage form of claim 60, wherein the gelling agent is in an effective amount to impart a viscosity of at least about 375 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

62. The controlled release oral solid dosage form of claim 60, wherein the gelling agent is in an effective amount to impart a viscosity of at least about 2,000 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

63. The controlled release oral solid dosage form of claim 60, wherein the gelling agent is in an effective amount to impart a viscosity from about 120 cP to about 5,000 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

64. The controlled release oral solid dosage form of claim 60, comprising from about 75 ng to about 750 mg hydrocodone bitartrate.

65. The controlled release oral solid dosage form of claim 60, comprising from about 2 mg to about 50 mg hydrocodone bitartrate.

66. A controlled release oral solid dosage form comprising a capsule containing:

(i) controlled release particles comprising a plurality of inert beads coated with hydrocodone bitartrate, the hydrocodone bitartrate coated beads overcoated with an ammonio methacrylate copolymer;

(ii) immediate release particles comprising a plurality of inert beads coated with hydrocodone bitartrate and hydroxypropylmethylcellulose; and

(iii) gelling agent particles comprising a plurality of inert beads coated with polyethylene oxide;

the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient, and having a viscosity of at least 120 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

67. The controlled release oral solid dosage form of claim 66, wherein the gelling agent particles and the controlled release particles have similar appearance.

68. The controlled release oral solid dosage form of claim 66, comprising from about 2 mg to about 50 mg hydrocodone bitartrate.

69. The controlled release oral solid dosage form of claim 66, wherein the gelling agent is in an effective amount to impart a viscosity of at least about 375 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.

70. The controlled release oral solid dosage form of claim 66, wherein the gelling agent is in an effective amount to impart a viscosity from about 120 cP to about 5,000 cP when the dosage form is subjected to tampering by dissolution in from about 0.5 to about 10 ml of an aqueous liquid.