PHARMACEUTICAL COMPOSITIONS RESISTANT TO ABUSE

• US 20140050787A1
• Filed: 10/24/2013
• Published: 02/20/2014
• Est. Priority Date: 02/06/2009
• Status: Active Grant

• Current Assignee: Egalet, Ltd. (Assertio Holdings, Inc.)
• Original Assignee: Egalet, Ltd. (Assertio Holdings, Inc.)
• Inventors: Tygesen, Peter Holm, Oevergaard, Jan Martin, Lindhardt, Karsten, Lyhne-Iversen, Louise Inoka, Olsen, Martin Rex, Haahr, Anne-Mette, Hoeyrup Hemmingsen, Pernille Kristine, Hoeilund-Jensen, Jocob Aas
• Granted Patent: US 9,168,228 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• 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 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• 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 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• 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 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• 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 9/2853 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 9/288 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/282
• CPC Class Codes: A61K 9/2893 Tablet coating processes mechanical aspects A61J3/06
• 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 9/4816 Wall or shell material
• CPC Class Codes: A61K 9/4833 : Encapsulating processes; Filling of capsules mechanical aspects A61J3/07

Abstract

The present invention provides immediate release pharmaceutical compositions for oral administration that are resistant to abuse.

Claims

1-44. -44. (canceled)

45. An abuse resistant pharmaceutical composition, the pharmaceutical composition comprising a shell resistant to physical tampering and a matrix composition,

wherein the matrix composition is at least partly contained within the shell and comprises an active drug substance,

wherein the shell comprises an outer shell wall having an inner surface and an outer surface, the outer surface being a double curved surface,

wherein the shell extends from a first end to a second end, the shell having a length in a range of from 4 mm to 20 mm,

wherein the outer shell wall has a first opening at the first end and a second opening at the second end, the first opening and the second opening having an area in a range of from about 1 mm² to about 100 mm², and

wherein the outer shell wall is of varying thickness and has a maximum thickness in a range of from 1.0 mm to about 10 mm, the outer shell wall being impermeable to water.

46. The pharmaceutical composition according to claim 45, wherein the shell comprises one or more reinforcement elements extending from the inner surface of the outer shell wall.

47. The pharmaceutical composition according to claim 46, wherein the one or more reinforcement elements comprises a first reinforcement wall.

48. The pharmaceutical composition according to claim 47, wherein the first reinforcement wall is a plane wall.

49. The pharmaceutical composition according to claim 47, wherein the first reinforcement wall is perpendicular to a first axis from the first end to the second end.

50. The pharmaceutical composition according to claim 47, wherein the first reinforcement wall is parallel to a first axis extending from the first end to the second end.

51. The pharmaceutical composition according to claim 47, wherein the first reinforcement wall has a thickness in a range of from 0.2 mm to 2 mm.

52. The pharmaceutical composition according to claim 47, wherein the first reinforcement wall has one or more openings.

53. The pharmaceutical composition according to claim 46, wherein the one or more reinforcement elements comprises a second reinforcement wall.

54. The pharmaceutical composition according to claim 53, wherein the second reinforcement wall is a plane wall.

55. The pharmaceutical composition according to claim 53, wherein the second reinforcement wall is perpendicular to a first axis extending from the first end to the second end.

56. The pharmaceutical composition according to claim 53, wherein the second reinforcement wall is parallel to a first axis extending from the first end to the second end.

57. The pharmaceutical composition according to claim 53, wherein the second reinforcement wall has a thickness in a range of from 0.2 mm to 2 mm.

58. The pharmaceutical composition according to claim 53, wherein the first reinforcement wall and the second reinforcement wall are parallel.

59. The pharmaceutical composition according to claim 58, wherein the first reinforcement wall and the second reinforcement wall extend in the same plane.

60. The pharmaceutical composition according to claim 53, wherein the first reinforcement wall intersects the second reinforcement wall forming an angle between the first reinforcement wall and the second reinforcement wall.

61. The pharmaceutical composition according to claim 45, wherein the shell defines a cavity extending from the first end to the second end and the matrix composition is at least partly contained within the cavity.

62. The pharmaceutical composition according to claim 45, wherein the shell defines a plurality of separated cavities extending from the first end to the second end and the matrix composition is at least partly contained within at least one of the plurality of separated cavities.

63. The pharmaceutical composition according to claim 62, wherein one or more of the cavities has a circular cross section perpendicular to a first axis extending from the first end to the second end.

64. The pharmaceutical composition according to claim 62, wherein one or more of the cavities has an elliptical cross section perpendicular to a first axis extending from the first end to the second end.

65. The pharmaceutical composition according to claim 45, wherein the outer surface of the shell has an elliptical cross section perpendicular to a first axis extending from the first end to the second end.

66. The pharmaceutical composition according to claim 45, wherein the outer surface of the shell forms an arc from the first end to the second end in a cross section along a first axis extending from the first end to the second end.

67. The pharmaceutical composition according to claim 45, wherein the shell comprises polylactic acid, and wherein the concentration of the polylactic acid in the shell is at least 50% w/w.

68. The pharmaceutical composition according to claim 45, wherein the shell comprises one or more polymers selected from the group consisting of ethyl cellulose grade 20, ethyl cellulose grade 100, cornpack 200, polycaprolactone, PEO 7000000, and polyhydroxybuturate.

69. The pharmaceutical composition according to claim 45, wherein the shell comprises one or more plasticizers selected from the group consisting of cetostearyl alcohol, castor oil, dibutyl sebacate, polyethylene oxide, and poloxamer.

70. The pharmaceutical composition according to claim 45, wherein the shell comprises a single polymer and the concentration of the polymer is in a range of from 5% to 100% w/w.

71. A pharmaceutical composition according to claim 45, wherein the shell comprises a mixture of polymers and the total concentration of polymers included in the shell is in a range of from 70% to 100% w/w.

72. The pharmaceutical composition according to claim 45, wherein the length of the outer shell wall is 16 mm.

73. The pharmaceutical composition according to claim 45, wherein the active drug substance comprises an analgesic selected from the group consisting of opioids, natural opium alkaloids, semi-synthetic opium alkaloids, morphine, opium, hydromorphone, nicomorphine, oxycodone, dihydrocodeine, diamorphine, papavereturn, codeine, phenylpiperidine derivatives, ketobemidone, pethidine, fentanyl, diphenylpropylamine derivatives, dextromoramide, piritramide, dextropropoxyphene, bezitramide, methadone, benzomorphan derivatives, pentazocine, phenazocine, oripavine derivatives, buprenorphine, morphinan derivatives, butorphanol, nalbuphine, tilidine, tramadol, dezocine, salicylic acid and derivatives, acetylsalicylic acid, aloxiprin, Choline salicylate, sodium salicylate, salicylamide, salsalate, ethenzamide, morpholine salicylate, dipyrocetyl, benorilate, diflunisal, potassium salicylate, guacetisal, carbasalate calcium, imidazole salicylate, pyrazolones, phenazone, metamizole sodium, aminophenazone, propyphenazone, nifenazone, anilides, paracetamol, phenacetin, bucetin, propacetamol, rimazolium, glafenine, floctafenine, viminol, nefopam, flupirtine, and ziconotide.

74. The pharmaceutical composition according to claim 45, wherein the active drug substance comprises one or more opioids selected from the group consisting of buprenorphine, codeine, dextromoramide, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, morphine, pentazocine, oxycodeine, oxycodone, oxymorphone, and tramadol, including pharmaceutically acceptable salts, molecular complexes, solvates, anhydrates, isomers, enantiomers, racemic mixtures, and mixtures thereof.

75. The pharmaceutical composition according to claim 74, wherein the one or more opioids are selected from the group consisting of hydrocodone, oxycodone, and morphine, including pharmaceutically acceptable salts, molecular complexes, solvates, anhydrates, isomers, enantiomers, racemic mixtures, and mixtures thereof.

76. The pharmaceutical composition according to claim 75, wherein the shell constitutes at least 40% v/v of the pharmaceutical composition.

77. The pharmaceutical composition according to claim 75, wherein the pharmaceutical composition is formulated and configured for oral administration.

78. The pharmaceutical composition according to claim 75, wherein the matrix composition comprises a polyethylene oxide polymer.

79. The pharmaceutical composition according to claim 78, wherein the matrix composition further comprises a block copolymer.

80. The pharmaceutical composition according to claim 75, wherein the matrix composition comprises one or more gelling agents.

81. The pharmaceutical composition according to claim 75, wherein the matrix composition comprises an antagonist or aversive agent.

82. The pharmaceutical composition according to claim 81, wherein the matrix composition comprises an inner core enclosing the antagonist or aversive agent.

83. The pharmaceutical composition according to claim 81, wherein the matrix composition comprises coated particles containing the antagonist or aversive agent.

84. A pharmaceutical composition according to any one of claims 78 and 79, wherein the polyethylene oxide polymer is selected from a polyethylene oxide having a molecular weight selected from a range falling within the group consisting of from 20,000 to 700,000 daltons, from 20,000 to 600,000 daltons, from 35,000 to 700,000 daltons, from 35,000 to 500,000 daltons, from 35,000 to 400,000 daltons, from 35,000 to 300,000 daltons, and from 50,000 to 300,000 daltons.

85. A pharmaceutical composition according to any one of claims 78 and 79, wherein the polyethylene oxide polymer is selected from a polyethylene oxide having a molecular weight selected from a range falling within the group consisting of at least 35,000 daltons, at least 50,000 daltons, at least 75,000 daltons, at least 100,000 daltons, at least 150,000 daltons, at least 200,000 daltons, at least 250,000 daltons, at least 300,000 daltons, and at least 400,000 daltons.