Claims for Patent: 8,765,167

Summary for Patent: 8,765,167

Title:	Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions
Abstract:	The present invention relates to water-soluble films incorporating anti-tacking agents and methods of their preparation. Anti-tacking agents may improve the flow characteristics of the compositions and thereby reduce the problem of film adhering to a user's mouth or to other units of film. In particular, the present invention relates to edible water-soluble delivery systems in the form of a film composition including a water-soluble polymer, an active component selected from cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof and at least one anti-tacking agent.
Inventor(s):	Myers; Garry L. (Kingsport, TN), Sanghvi; Pradeep (Schererville, IN), Verrall; Andrew Philip (Crown Point, IN), Francis; Vimala (Fremont, CA), Moss; Laura (Schererville, IN)
Assignee:	MonoSol Rx, LLC (Portage, IN)
Application Number:	11/517,982
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,765,167
Patent Claims:	1. An oral film for delivery of a desired amount of an active component comprising: an ingestible, water-soluble, polymer matrix; at least one anti-tacking agent selected from the group consisting of stearates; stearic acid; vegetable oil; waxes; a blend of magnesium stearate and sodium lauryl sulfate; boric acid; surfactants; sodium benzoate; sodium acetate; sodium chloride; DL-Leucine; polyethylene glycol; sodium oleate; sodium lauryl sulfate; magnesium lauryl sulfate; talc; corn starch; amorphous silicon dioxide; syloid; metallic stearates, Vitamin E, Vitamin E TPGS, silica and combinations thereof; and a substantially uniform distribution of said desired amount of said active component within said polymer matrix, wherein said active component is selected from the group consisting of cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof, said film being formed by a controlled drying process which rapidly forms a viscoelastic matrix to lock-in said active in place within said matrix and maintain said substantially uniform distribution; wherein said film is self-supporting and the active component is substantially uniformly distributed, whereby said substantially uniform distribution is measured by substantially equally sized individual unit doses which do not vary by more than 10% of said desired amount of said active component. 2. The film of claim 1, wherein said anti-tacking agent comprises magnesium stearate. 3. The film of claim 2, wherein said anti-tacking agent further comprises silica. 4. The film of claim 1, wherein said anti-tacking agent is present in amounts of about 0.01% to about 20% by weight of said delivery system. 5. The film of claim 1, wherein said anti-tacking agent comprises: magnesium stearate present in amounts of about 0.1% to about 2.5% by weight of said delivery system; and silica present in amounts of about 0.1% to about 1.5% by weight of said delivery system. 6. The film of claim 1, wherein said water-soluble polymer matrix comprises polyethylene oxide and a cellulosic polymer. 7. The film of claim 6, wherein said cellulosic polymer comprises hydroxypropyl cellulose. 8. The film of claim 6, wherein said cellulosic polymer comprises hydroxypropylmethyl cellulose. 9. The film of claim 1, wherein said active component comprises dextromethorphan. 10. The film of claim 1, further comprising polydextrose. 11. The film of claim 1, wherein said film is applied to an oral cavity of a mammal. 12. The film of claim 11, wherein said film adheres to the tongue or the buccal cavity of the mammal. 13. An oral film for delivery of a desired amount of an active component comprising: an ingestible, water-soluble polymer matrix comprising at least one polymer selected from the group consisting of hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, polyethylene oxide and combinations thereof; a substantially uniform distribution of said desired amount of said active component within said polymer matrix, wherein said active component is selected from the group consisting of cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof said film being formed by a controlled drying process which rapidly forms a viscoelastic matrix to lock-in said active in place within said matrix and maintain said substantially uniform distribution; and an anti-tacking agent selected from the group consisting of Vitamin E, Vitamin E TPGS, and sodium benzoate, wherein said anti-tacking agent is present in amounts of about 0.01% to about 20% by weight of said film; wherein said film is self-supporting and the active component is substantially uniformly distributed, whereby said substantially uniform distribution is measured by substantially equal sized individual unit doses which do not vary by more than 10% of said desired amount of said active component. 14. An oral film for delivery of a desired amount of an active component comprising: an ingestible, water-soluble polymer matrix comprising polyethylene oxide in combination with a polymer selected from the group consisting of hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, and combinations thereof; and an anti-tacking agent selected from the group consisting of Vitamin E, Vitamin E TPGS, and sodium benzoate, wherein said anti-tacking agent is present in amounts sufficient to provide anti-tacking and therapeutic properties, and a substantially uniform distribution of said desired amount of said active component within said polymer matrix, said film being formed by a controlled drying process which rapidly forms a viscoelastic matrix to lock-in said active in place within said matrix and maintain said substantially uniform distribution; wherein said film is self-supporting and the active component is substantially uniformly distributed, whereby said substantially uniform distribution is measured by substantially equal sized individual unit doses which do not vary by more than 10% of said desired amount of said active component. 15. An oral film for delivery of a desired amount of an active component comprising: an ingestible, water-soluble polymer matrix comprising polyethylene oxide and a polymer selected from the group consisting of hydroxypropyl cellulose, hydroxyethyl cellulose, and carboxymethyl cellulose; and polydextrose, wherein said polyethylene oxide, said polymer selected from the group consisting of hydroxypropyl cellulose, hydroxyethyl cellulose, and carboxymethyl cellulose, and said polydextrose are present in a ratio of about 45:45:10 by weight; a substantially uniform distribution of said desired amount of said active component within said polymer matrix, wherein said active component is selected from the group consisting of cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof; said film being formed by a controlled drying process which rapidly forms a viscoelastic matrix to lock-in said active in place within said matrix and maintain said substantially uniform distribution; at least one anti-tacking agent selected from the group consisting of stearates; stearic acid; vegetable oil; waxes; a blend of magnesium stearate and sodium lauryl sulfate; boric acid; surfactants; sodium benzoate; sodium acetate; sodium chloride; DL-Leucine; polyethylene glycol; sodium oleate; sodium lauryl sulfate; magnesium lauryl sulfate; talc; corn starch; amorphous silicon dioxide; syloid; metallic stearates, Vitamin E, Vitamin E TPGS, silica and combinations thereof; and wherein said film is self-supporting and the active component is substantially uniformly distributed, whereby said substantially uniform distribution is measured by substantially equal sized individual unit doses which do not vary by more than 10% of said desired amount of said active component. 16. An oral film for delivery of a desired amount of an active component comprising: (a) a self-supporting film having at least one surface, said film comprising: (i) an ingestible, water-soluble polymer matrix; and (ii) a substantially uniform distribution of said desired amount of said active component within said polymer matrix, wherein said active component is selected from the group consisting of cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof; said film being formed by a controlled drying process which rapidly forms a viscoelastic matrix to lock-in said active in place within said matrix and maintain said substantially uniform distribution; and (b) a coating on said at least one surface of said self-supporting film, said coating comprising at least one anti-tacking agent selected from the group consisting of stearates; stearic acid; vegetable oil; waxes; a blend of magnesium stearate and sodium lauryl sulfate; boric acid; surfactants; sodium benzoate; sodium acetate; sodium chloride; DL-Leucine; polyethylene glycol; sodium oleate; sodium lauryl sulfate; magnesium lauryl sulfate; talc; cornstarch; amorphous silicon dioxide; syloid; metallic stearates, Vitamin E, Vitamin E TPGS, silica and combinations thereof; and wherein said film is self-supporting and the active component is substantially uniformly distributed, whereby said substantially uniform distribution is measured by substantially equal sized individual unit doses which do not vary by more than 10% of said desired amount of said active component. 17. A multi-layer film for delivery of a desired amount of an active component comprising: (a) at least one first film layer comprising: (i) an ingestible, water-soluble polymer matrix; and (ii) at least one anti-tacking agent selected from the group consisting of stearates; stearic acid; vegetable oil; waxes; a blend of magnesium stearate and sodium lauryl sulfate; boric acid; surfactants; sodium benzoate; sodium acetate; sodium chloride; DL-Leucine; polyethylene glycol; sodium oleate; sodium lauryl sulfate; magnesium lauryl sulfate; talc; corn starch; amorphous silicon dioxide; syloid; metallic stearates, Vitamin E, Vitamin E TPGS, silica and combinations thereof; and (b) a second film layer comprising: (i) an ingestible, water-soluble polymer matrix; and (ii) a substantially uniform distribution of said desired amount of said active component within said polymer matrix, wherein said active component is selected from the group consisting of cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof, wherein said first film layer is substantially in contact with said second film layer; said film being formed by a controlled drying process which rapidly forms a viscoelastic matrix to lock-in said active in place within said matrix and maintain said substantially uniform distribution; and wherein said film is self-supporting and the active component is substantially uniformly distributed, whereby said substantially uniform distribution is measured by substantially equal sized individual unit doses which do not vary by more than 10% of said desired amount of said active component. 18. The multi-layer film of claim 17, wherein said first film layer is laminated to said second film layer. 19. A process for making a self-supporting film having a substantially uniform distribution of components for delivery of a desired amount of an active component comprising: (a) combining an edible, water-soluble polymer, a solvent, an active component selected from the group consisting of cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof and at least one anti-tacking agent to form a matrix with a substantially uniform distribution of said components; (b) forming a self-supporting film from said matrix; said film having a substantially uniform distribution of said desired amount of said active component within said matrix, whereby said substantially uniform distribution of said active component is measured by substantially equal sized individual unit doses which do not vary by more than 10% of said desired amount of said active component; (c) providing a surface having top and bottom sides; (d) feeding said film onto said top side of said surface; and (e) drying said film by applying heat to said bottom side of said surface. 20. The process of claim 19, wherein said anti-tacking agent comprises Vitamin E TPGS. 21. The process of claim 19, wherein said anti-tacking agent comprises magnesium stearate and silica. 22. The process of claim 19, wherein said matrix further comprises polydextrose. 23. The process of claim 19, wherein said film is ingestible. 24. The process of claim 19, wherein said film is flexible when dried. 25. The process of claim 19, wherein step (e) comprises applying hot air currents to said bottom side of said surface with substantially no top air flow. 26. The film of claim 1, wherein the anti-tacking agent is present in an amount sufficient to impart reduced film-to-film coefficient of friction. 27. The film of claim 1, wherein said film has a coefficient of friction which is low enough to reduce adhesion of said film to the roof of a mouth of a user of said film upon placement into the user's mouth. 28. The film of claim 15, wherein the anti-tacking agent is present in an amount sufficient to yield a film with a coefficient of friction which reduces adhesion of the film to adjacent surfaces during processing. 29. The film of claim 15, said film having a coefficient of friction which is low enough to reduce adhesion of said film to the roof of a mouth of a user of said film upon placement into the user's mouth. 30. The film of claim 17, wherein the anti-tacking agent is present in an amount sufficient to yield a film with a coefficient of friction which reduces adhesion of the film to adjacent surfaces during processing. 31. The film of claim 17, said film having a coefficient of friction which is low enough to reduce adhesion of said film to the roof of a mouth of a user of said film upon placement into the user's mouth. 32. The film of claim 6, wherein said cellulosic polymer comprises hydroxyethyl cellulose. 33. The film of claim 13, wherein said at least one polymer is hydroxyethyl cellulose. 34. The film of claim 14, wherein said water-soluble polymer matrix comprises polyethylene oxide in combination with hydroxyethyl cellulose. 35. The film of claim 15, wherein said water-soluble polymer matrix comprises polyethylene oxide and hydroxyethyl cellulose. 36. The film of claim 16, wherein said water-soluble polymer matrix comprises hydroxyethyl cellulose. 37. The process of claim 18, wherein said water-soluble polymer comprises hydroxyethyl cellulose. 38. The film of claim 6, wherein said cellulosic polymer comprises carboxymethyl cellulose. 39. The film of claim 13, wherein said at least one polymer is carboxymethyl cellulose. 40. The film of claim 14, wherein said water-soluble polymer matrix comprises polyethylene oxide in combination with carboxymethyl cellulose. 41. The film of claim 15, wherein said polymer matrix comprises polyethylene oxide and carboxymethyl cellulose. 42. The film of claim 16, wherein said water-soluble polymer matrix comprises carboxymethyl cellulose. 43. The process of claim 19, wherein said water-soluble polymer comprises carboxymethyl cellulose. 44. The film of claim 1, further comprising a buffer. 45. The film of claim 13, further comprising a buffer. 46. The film of claim 14, further comprising a buffer. 47. The film of claim 15, further comprising a buffer. 48. The film of claim 16, further comprising a buffer. 49. The film of claim 17, said at least one first film layer or said second film layer further comprising a buffer. 50. The process of claim 19, further comprising combining a buffer with said edible, water-soluble polymer, said solvent, and said active component. 51. The film of claim 1, further comprising a sweetener. 52. The film of claim 13, further comprising a sweetener. 53. The film of claim 14, further comprising a sweetener. 54. The film of claim 15, further comprising a sweetener. 55. The film of claim 16, further comprising a sweetener. 56. The film of claim 17, said at least one first film layer or said second film layer further comprising a sweetener. 57. The process of claim 19, further comprising combining a sweetener with said edible, water-soluble polymer, said solvent, and said active component. 58. The film of claim 51, wherein said sweetener is Acesulfame-K. 59. The film of claim 52, wherein said sweetener is Acesulfame-K. 60. The film of claim 53, wherein said sweetener is Acesulfame-K. 61. The film of claim 54, wherein said sweetener is Acesulfame-K. 62. The film of claim 55, wherein said sweetener is Acesulfame-K. 63. The film of claim 56, wherein said sweetener is Acesulfame-K. 64. The process of claim 57, wherein said sweetener is Acesulfame-K. 65. The film of claim 1, further comprising a flavoring agent. 66. The film of claim 13, further comprising a flavoring agent. 67. The film of claim 15, further comprising a flavoring agent. 68. The film of claim 15, further comprising a flavoring agent. 69. The film of claim 16, further comprising a flavoring agent. 70. The film of claim 17, said at least one first film layer or said second film layer further comprising a flavoring agent. 71. The process of claim 19, further comprising combining a flavoring agent with said edible, water-soluble polymer, said solvent, and said active component. 72. The film of claim 1, further comprising a coloring agent. 73. The film of claim 13, further comprising a coloring agent. 74. The film of claim 14, further comprising a coloring agent. 75. The film of claim 15, further comprising a coloring agent. 76. The film of claim 16, further comprising a coloring agent. 77. The film of claim 17, said at least one first film layer or said second film layer further comprising a coloring agent. 78. The process of claim 19, further comprising a coloring agent in said self-supporting film. 79. The process of claim 19, wherein said anti-tacking agent comprises Vitamin E. 80. The film of claim 17, wherein said water-soluble polymer matrix in said first film layer and/or in said second film layer comprises hydroxyethyl cellulose. 81. The film of claim 17, wherein said water-soluble polymer matrix in said first film layer and/or in said second film layer comprises carboxymethyl cellulose. 82. The film of claim 1, wherein the anti-tacking agent comprises sodium benzoate. 83. The film of claim 13, wherein the anti-tacking agent comprises sodium benzoate. 84. The film of claim 14, wherein the anti-tacking agent comprises sodium benzoate. 85. The film of claim 15, wherein the anti-tacking agent comprises sodium benzoate. 86. The film of claim 16, wherein the anti-tacking agent comprises sodium benzoate. 87. The film of claim 17, wherein the anti-tacking agent comprises sodium benzoate. 88. The film of claim 19, wherein the anti-tacking agent comprises sodium benzoate. 89. The film of claim 13, wherein the active component comprises an active selected from the group consisting of an opiate, opiate derivative, analgesic and combinations thereof. 90. The film of claim 14, wherein the active component comprises an active selected from the group consisting of an opiate, opiate derivative, analgesic and combinations thereof. 91. The film of claim 15, wherein the active component comprises an active selected from the group consisting of an opiate, opiate derivative, analgesic and combinations thereof. 92. The film of claim 16, wherein the active component comprises an active selected from the group consisting of an opiate, opiate derivative, analgesic and combinations thereof. 93. The film of claim 17, wherein the active component comprises an active selected from the group consisting of an opiate, opiate derivative, analgesic and combinations thereof. 94. The film of claim 19, wherein the active component comprises an active selected from the group consisting of an opiate, opiate derivative, analgesic and combinations thereof. 95. An oral film for delivery of a desired amount of an active component comprising: an ingestible, water-soluble polymer matrix comprising a polymer selected from the group consisting of hydroxyethylcellulose, hydroxypropylcellulose and carboxymethyl cellulose and combinations thereof; at least one anti-tacking agent comprising sodium benzoate; a substantially uniform distribution of said desired amount of said active component within said polymer matrix, wherein said active component is selected from the group consisting of cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof, said film being formed by a controlled drying process which rapidly forms a viscoelastic matrix to lock-in said active in place within said matrix and maintain said substantially uniform distribution; wherein said film is self-supporting and the active component is substantially uniformly distributed, whereby said substantially uniform distribution is measured by substantially equally sized individual unit doses which do not vary by more than 10% of said desired amount of said active component. 96. The film of claim 95, further comprising a component selected from the group consisting of citric acid, propylene glycol, a sweetener, a preservative, a coloring agent, a flavor and combinations thereof. 97. The film of claim 95 further comprising an opiate or opiate derivative. 98. The film of claim 95 further comprising an analgesic. 99. The film of claim 95 further comprising an opiate or opiate derivative and an analgesic. 100. The film of claim 95 further comprising vitamin E acetate. 101. The film of claim 95 further comprising titanium dioxide. 102. The film of claim 96 wherein the flavor comprises peppermint oil. 103. The film of claim 95 further comprising a buffer. 104. The film of claim 96 wherein the sweetener comprises Acesufame K. 105. The film of claim 95 further comprising an oxide filler. 106. The film of claim 95 wherein the active is taste-masked. 107. The film of claim 96 wherein the sweetener comprises sodium saccharin. 108. The film of claim 95 further comprising polyacrylic acid. 109. An oral film for delivery of a desired amount of an active component comprising: an ingestible, water-soluble polymer matrix comprising a polymer selected from the group consisting of hydroxyethylcellulose, hydroxypropylcellulose, carboxymethyl cellulose and combinations thereof; at least one anti-tacking agent comprising sodium benzoate; an active component selected from the group consisting of an opiate, opiate derivative, an analgesic and combinations thereof; a sweetener comprising sodium saccharin; flavor comprising peppermint oil; vitamin E acetate; a metal oxide; and a buffer; wherein said active component is selected from the group consisting of cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof, said film being formed by a controlled drying process which rapidly forms a viscoelastic matrix to lock-in said active in place within said matrix to maintain a substantially uniform distribution thereof; wherein said film is self-supporting and the active component is substantially uniformly distributed, whereby said substantially uniform distribution is measured by substantially equally sized individual unit doses which do not vary by more than 10% of said desired amount of said active component. 110. A multi-layer film for delivery of a desired amount of an active component comprising: (a) a first film layer comprising: (i) an ingestible, water-soluble or water-swellable polymer matrix; and (b) at least a second film layer comprising: (i) an ingestible, water-soluble or water-swellable polymer matrix comprising a water-soluble or swellable polymer; wherein the first and/or second layers further comprise: a desired amount of a substantially uniformly distributed active component, said active component being selected from the group consisting of cosmetic agents, pharmaceutical agents, vitamins, bioactive agents and combinations thereof; a component selected from the group consisting of an anti-tacking agent, a sweetener, a flavor, an acidulent, an oxide filler, propylene glycol, vitamin E acetate, polyacrylic acid, a preservative, a buffer, a coloring agent and combinations thereof; and wherein said first film layer is substantially in contact with said second film layer; said film being formed by a controlled drying process which rapidly forms a viscoelastic matrix to lock-in said active component in place and maintain said substantially uniform distribution; and wherein said film is self-supporting, whereby said substantially uniform distribution of said active component is measured by substantially equal sized individual unit doses which do not vary by more than 10% of said desired amount of said active component. 111. The multi-layer film of claim 110, wherein the sweetener comprises sodium saccharin. 112. The multi-layer film of claim 110, wherein the flavor comprises peppermint oil. 113. The multi-layer film of claim 110, wherein the acidulent comprises citric acid. 114. The multi-layer film of claim 110, wherein the active is selected from the group consisting of opiates, opiate derivatives, analgesics and combinations thereof. 115. The multi-layer film of claim 110, further comprising sodium benzoate. 116. The multi-layer film of claim 110, wherein the water-soluble or water-swellable polymer matrix comprises a polymer selected from the group consisting of hydroxyethylcellulose, hydroxypropylcellulose, carboxymethyl cellulose and combinations thereof. 117. The film of claim 13, wherein the anti-tacking agent is present in an amount sufficient to impart reduced film-to-film coefficient of friction. 118. The film of claim 13, wherein the anti-tacking agent is present in an amount sufficient to yield a film with a coefficient of friction which reduces adhesion of the film to adjacent surfaces during processing. 119. The film of claim 14, wherein the anti-tacking agent is present in an amount sufficient to impart reduced film-to-film coefficient of friction. 120. The film of claim 14, wherein the anti-tacking agent is present in an amount sufficient to yield a film with a coefficient of friction which reduces adhesion of the film to adjacent surfaces during processing. 121. The film of claim 15, wherein the anti-tacking agent is present in an amount sufficient to impart reduced film-to-film coefficient of friction. 122. The film of claim 16, wherein the anti-tacking agent is present in an amount sufficient to impart reduced film-to-film coefficient of friction. 123. The film of claim 16, wherein the anti-tacking agent is present in an amount sufficient to yield a film with a coefficient of friction which reduces adhesion of the film to adjacent surfaces during processing. 124. The film of claim 17, wherein the anti-tacking agent is present in an amount sufficient to impart reduced film-to-film coefficient of friction. 125. The film of claim 1, wherein the active component comprises an opiate, opiate derivative, an analgesic and combinations thereof. 126. The film of claim 1, further comprising a preservative. 127. The film of claim 1, wherein the film is sufficient to impart reduced film-to-film coefficient of friction.