Polyethylene-oxide based films and drug delivery systems made therefrom

US 7,897,080 B2
Filed: 11/09/2009
Issued: 03/01/2011
Est. Priority Date: 10/12/2001
Status: Expired due to Fees

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First Claim

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1. A process for making a film having a substantially uniform distribution of components, comprising the steps of:

(a) forming a masterbatch pre-mix comprising a solvent and a polymer selected from the group consisting of water-soluble polymers, water-swellable polymers and combinations thereof;

(b) adding an active to a pre-determined amount of said masterbatch pre-mix to form a flowable polymer matrix, said matrix having a substantially uniform distribution of said active;

(c) casting said flowable polymer matrix;

(d) evaporating at least a portion of said solvent from said flowable polymer matrix to form a visco-elastic film within about 10 minutes or fewer to maintain said substantially uniform distribution of said active by locking-in or substantially preventing migration of said active within said visco-elastic film; and

(e) forming a resulting film from said visco-elastic film, wherein said resulting film has a water content of 10% or less and said substantially uniform distribution of active by said locking-in or substantially preventing migration of said active is maintained.

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Abstract

The invention relates to the film products and methods of their preparation that demonstrate a non-self-aggregating uniform heterogeneity. Desirably, the films disintegrate in water and may be formed by a controlled drying process, or other process that maintains the required uniformity of the film. The films contain a polymer component, which includes polyethylene oxide optionally blended with hydrophilic cellulosic polymers. Desirably, the films also contain a pharmaceutical and/or cosmetic active agent with no more than a 10% variance of the active agent pharmaceutical and/or cosmetic active agent per unit area of the film.

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299 Claims

1. A process for making a film having a substantially uniform distribution of components, comprising the steps of:
- (a) forming a masterbatch pre-mix comprising a solvent and a polymer selected from the group consisting of water-soluble polymers, water-swellable polymers and combinations thereof;
  
  (b) adding an active to a pre-determined amount of said masterbatch pre-mix to form a flowable polymer matrix, said matrix having a substantially uniform distribution of said active;
  
  (c) casting said flowable polymer matrix;
  
  (d) evaporating at least a portion of said solvent from said flowable polymer matrix to form a visco-elastic film within about 10 minutes or fewer to maintain said substantially uniform distribution of said active by locking-in or substantially preventing migration of said active within said visco-elastic film; and
  
  (e) forming a resulting film from said visco-elastic film, wherein said resulting film has a water content of 10% or less and said substantially uniform distribution of active by said locking-in or substantially preventing migration of said active is maintained.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 297)
- - 2. The process of claim 1, wherein said pre-determined amount of master batch pre-mix is controllably fed via a first metering pump and a control valve to a first mixer and a second mixer.
  - 3. The process of claim 2, wherein said first mixer and said second mixer are arranged in parallel, series or a combination thereof.
  - 4. The process of claim 1, wherein said water-soluble polymer comprises polyethylene oxide.
  - 5. The process of claim 1, wherein said polymer comprises a polymer selected from the group consisting of cellulose, a cellulose derivative, pullulan, polyvinyl pyrrolidone, polyvinyl alcohol, polyethylene glycol, carboxyvinyl copolymers, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, sodium alginate, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, and combinations thereof, alone or in combination with polyethylene oxide.
  - 6. The process of claim 5, wherein said polymer further comprises a water insoluble polymer selected from the group consisting of ethylcellulose, hydroxypropyl ethyl cellulose, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, polyvinylacetatephthalates, phthalated gelatin, crosslinked gelatin, poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polycaprolactone and combinations thereof.
  - 7. The process of claim 5, wherein said polymer further comprises a polymer selected from the group consisting of methylmethacrylate copolymer, polyacrylic acid polymer, poly(glycolic acid) (PGA), poly(lactic acid) (PLA), poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polydioxanones, polyoxalates, poly({acute over (α
    - )}-esters), polyanhydrides, polyacetates, polycaprolactones, poly(orthoesters), polyamino acids, polyaminocarbonates, polyurethanes, polycarbonates, polyamides, poly(alkyl cyanoacrylates), and mixtures and copolymers thereof.
  - 8. The process of claim 5, wherein said polymer further comprises a polymer selected from the group consisting of sodium alginate, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, starch, gelatin, carageenan, locust bean gum, dextran, gellan gum and combinations thereof.
  - 9. The process of claim 5, wherein said polymer further comprises a polymer selected from the group consisting of ethylcellulose, hydroxypropyl ethyl cellulose, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, polyvinylacetatephthalates, phthalated gelatin, crosslinked gelatin, poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polycaprolactone, methylmethacrylate copolymer, polyacrylic acid polymer, poly(glycolic acid) (PGA), poly(lactic acid) (PLA), poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polydioxanones, polyoxalates, poly(d-esters), polyanhydrides, polyacetates, polycaprolactones, poly(orthoesters), polyamino acids, polyaminocarbonates, polyurethanes, polycarbonates, polyamides, poly(alkyl cyanoacrylates), sodium alginate, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, starch, gelatin, carageenan, locust bean gum, dextran, gellan gum and combinations thereof.
  - 10. The process of claim 1, wherein said solvent is selected from the group consisting of water, polar organic solvent, and combinations thereof.
  - 11. The process of claim 10, wherein said solvent is selected from the group consisting of ethanol, isopropanol, acetone, and combinations thereof.
  - 12. The process of claim 1, wherein said active is selected from the group consisting of bioactive active, pharmaceutical actives, drugs, medicaments and combinations thereof.
  - 13. The process of claim 1, wherein said active is selected from the group consisting of ace-inhibitors, anti-anginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, analgesics, anesthetics, anti-convulsants, anti-depressants, anti-diabetic agents, anti-diarrhea preparations, antidotes, anti-histamines, anti-hypertensive drugs, anti-inflammatory agents, anti-lipid agents, anti-manics, anti-nauseants, anti-stroke agents, anti-thyroid preparations, anti-tumor drugs, anti-viral agents, acne drugs, alkaloids, amino acid preparations, anti-tussives, anti-uricemic drugs, anti-viral drugs, anabolic preparations, systemic and non-systemic anti-infective agents, anti-neoplastics, anti-parkinsonian agents, anti-rheumatic agents, appetite stimulants, blood modifiers, bone metabolism regulators, cardiovascular agents, central nervous system stimulates, cholinesterase inhibitors, contraceptives, decongestants, dietary supplements, dopamine receptor agonists, endometriosis management agents, enzymes, erectile dysfunction therapies, fertility agents, gastrointestinal agents, homeopathic remedies, hormones, hypercalcemia and hypocalcemia management agents, immunomodulators, immunosuppressives, migraine preparations, motion sickness treatments, muscle relaxants, obesity management agents, osteoporosis preparations, oxytocics, parasympatholytics, parasympathomimetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, smoking cessation aids, sympatholytics, tremor preparations, urinary tract agents, vasodilators, laxatives, antacids, ion exchange resins, anti-pyretics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, psycho-tropics, stimulants, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, anti-tumor drugs, anti-coagulants, anti-thrombotic drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo-glycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, uterine relaxants, anti-obesity drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof.
  - 14. The process of claim 1, wherein said active is selected from the group consisting of cosmetic actives, antigens, allergens, spores, microorganisms, seeds, mouthwash components, flavors, fragrances, enzymes, preservatives, sweetening agents, colorants, spices, vitamins and combinations thereof.
  - 15. The process of claim 1, wherein said active is a bioactive active.
  - 16. The process of claim 1, wherein said active is a biological response modifier.
  - 17. The process of claim 1, wherein said active is an opiate or opiate-derivative.
  - 18. The process of claim 1, wherein said active is an anti-emetic.
  - 19. The process of claim 1, wherein said active is an amino acid preparation.
  - 20. The process of claim 1, wherein said active is selected from the group consisting of sildenafils, tadalafils, vardenafils, apomorphines, yohimbine hydrochlorides, alprostadils and combinations thereof.
  - 21. The process of claim 1, wherein said active is a protein.
  - 22. The process of claim 1, wherein said active is insulin.
  - 23. The process of claim 1, wherein said active is an anti-diabetic.
  - 24. The process of claim 1, wherein said active is an antihistamine.
  - 25. The process of claim 1, wherein said active is an anti-tussive.
  - 26. The process of claim 1, wherein said active is a non-steroidal anti-inflammatory.
  - 27. The process of claim 1, wherein said active is an anti-asthmatics.
  - 28. The process of claim 1, wherein said active is an anti-diarrhea.
  - 29. The process of claim 1, wherein said active is an alkaloid.
  - 30. The process of claim 1, wherein said active is an anti-psychotic.
  - 31. The process of claim 1, wherein said active is an anti-spasmodic.
  - 32. The process of claim 1, wherein said active is a biological response modifier.
  - 33. The process of claim 1, wherein said active is an anti-obesity drug.
  - 34. The process of claim 1, wherein said active is an H₂-antagonist.
  - 35. The process of claim 34, wherein said H₂-antagonist is selected from the group consisting of cimetidine, ranitidine hydrochloride, famotidine, nizatidine, ebrotidine, mifentidine, roxatidine, pisatidine, aceroxatidine and combinations thereof.
  - 36. The process of claim 1, wherein said active is a smoking cessation aid.
  - 37. The process of claim 1, wherein said active is an anti-parkinsonian agent.
  - 38. The process of claim 1, wherein said active is an anti-depressant.
  - 39. The process of claim 1, wherein said active is an anti-migraine.
  - 40. The process of claim 1, wherein said active is an anti-Alzheimer'"'"'s agents.
  - 41. The process of claim 1, wherein said active is a dopamine receptor agonist.
  - 42. The process of claim 1, wherein said active is a cerebral dilator.
  - 43. The process of claim 1, wherein said active is a psychotherapeutic agent.
  - 44. The process of claim 1, wherein said active is an antibiotic.
  - 45. The process of claim 1, wherein said active is an anesthetic.
  - 46. The process of claim 1, wherein said active is a contraceptive.
  - 47. The process of claim 1, wherein said active is an anti-thrombotic drug.
  - 48. The process of claim 1, wherein said active is diphenhydramine.
  - 49. The process of claim 1, wherein said active is nabilone.
  - 50. The process of claim 1, wherein said active is albuterol sulfate.
  - 51. The process of claim 1, wherein said active is an anti-tumor drug.
  - 52. The process of claim 1, wherein said active is a glycoprotein.
  - 53. The process of claim 1, wherein said active is an analgesic.
  - 54. The process of claim 1, wherein said active is a hormone.
  - 55. The process of claim 1, wherein said active is a decongestant.
  - 56. The process of claim 1, wherein said active is a loratadine.
  - 57. The process of claim 1, wherein said active is dextromethorphan.
  - 58. The process of claim 1, wherein said active is chlorpheniramine maleate.
  - 59. The process of claim 1, wherein said active is selected from the group consisting of an analgesic, an anti-inflammatory, an antihistamine, a decongestant, a cough suppressant and combinations thereof.
  - 60. The process of claim 1, wherein said active is an appetite stimulant.
  - 61. The process of claim 1, wherein said active is a gastrointestinal agent.
  - 62. The process of claim 1, wherein said active is a hypnotic.
  - 63. The process of claim 1, wherein said active is taste-masked.
  - 64. The process of claim 1, wherein said active is taste-masked using a flavor.
  - 65. The process of claim 1, wherein said active is coated with a controlled release composition.
  - 66. The process of claim 65, wherein said controlled release composition provides an immediate release.
  - 67. The process of claim 65, wherein said controlled release composition provides a delayed release.
  - 68. The process of claim 65, wherein said controlled release composition provides a sustained release.
  - 69. The process of claim 65, wherein said controlled release composition provides a sequential release.
  - 70. The process of claim 1, wherein said active is a particulate.
  - 71. The process of claim 1, further comprising adding a degassing agent to said masterbatch premix.
  - 72. The process of claim 1, further comprising a step of providing a second film layer.
  - 73. The process of claim 72, wherein said second film layer is coated onto said resulting film.
  - 74. The process of claim 72, wherein said second film layer is spread onto said resulting film.
  - 75. The process of claim 72, wherein said second film layer is cast onto said resulting film.
  - 76. The process of claim 72, wherein said second film layer is extruded onto said resulting film.
  - 77. The process of claim 72, wherein said second film layer is sprayed onto said resulting film.
  - 78. The process of claim 72, wherein said second film layer is laminated onto said resulting film.
  - 79. The process of claim 72, further comprising laminating said resulting film to another film.
  - 80. The process of claim 72, wherein said second film comprises an active.
  - 81. The process of claim 72, wherein said active in said second film is different than said active in said resulting film.
  - 243. The process of claim 1, said active is an anti-nauseant.
  - 244. The process of claim 1, said active is an erectile dysfunction.
  - 245. The process of claim 1, said active is a vasoconstrictor.
  - 246. The process of claim 1, said active is a stimulant.
  - 247. The process of claim 1, said active is a migraine treatment.
  - 248. The process of claim 1, said active is granisetron hydrochloride.
  - 249. The process of claim 1, wherein said resulting film provides administration of said active to an individual through the buccal cavity of said individual.
  - 250. The process of claim 1, wherein said resulting film provides administration of said active through gingival application of said individual.
  - 251. The process of claim 1, wherein said resulting film provides administration of said active through sublingual application of said individual.
  - 252. The process of claim 1, wherein said resulting film provides administration of said active to an individual through a mucosal membrane of said individual.
  - 253. The process of claim 1, wherein said resulting film provides administration of said active to an individual by administration within the body of the individual during surgery.
  - 254. The process of claim 1, wherein said resulting film has a variation of active content of less than 10% per film unit.
  - 255. The process of claim 1, further comprising the step of forming a plurality of individual dosage units of substantially the same size, wherein the active content of individual dosage units has a variance of no more than 10%.
  - 256. The method of claim 1, wherein said resulting film contains less than about 6% by weight solvent.
  - 257. The method of claim 1, wherein said at least one edible polymer, said active, and said at least one polar solvent are each ingestible materials.
  - 258. The method of claim 1, wherein said resulting film is orally administrable.
  - 259. The method of claim 1, wherein said active is in the form of a particle.
  - 260. The method of claim 1, wherein said matrix comprises a dispersion.
  - 297. The method of claim 1, wherein said matrix comprises an emulsion, a colloid or a suspension.

82. A process for making a film having a substantially uniform distribution of components, comprising the steps of:
- (a) forming a flowable polymer matrix comprising a polymer selected from the group consisting of a water-soluble polymer, a water swellable polymer and combinations thereof, a solvent and an active selected from the group consisting of bioactive actives, pharmaceutical actives, drugs, medicaments and combinations thereof, said matrix having a substantially uniform distribution of said active;
  
  (b) casting said flowable polymer matrix;
  
  (c) evaporating at least a portion of said solvent from said flowable polymer matrix to form a visco-elastic film within about 10 minutes or fewer to maintain said substantially uniform distribution of said active by locking-in or substantially preventing migration of said active within said visco-elastic film; and
  
  (d) forming a resulting film from said visco-elastic film, wherein said resulting film has a water content of 10% or less and said substantially uniform distribution of active by said locking-in or substantially preventing migration of said active is maintained.
- View Dependent Claims (83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 298)
- - 83. The process of claim 82, wherein said water-soluble polymer comprises polyethylene oxide.
  - 84. The process of claim 82, wherein said polymer comprises a polymer selected from the group consisting of cellulose, a cellulose derivative, pullulan, polyvinyl pyrrolidone, polyvinyl alcohol, polyethylene glycol, carboxyvinyl copolymers, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, sodium alginate, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, and combinations thereof, alone or in combination with polyethylene oxide.
  - 85. The process of claim 84, wherein said polymer further comprises a water insoluble polymer selected from the group consisting of ethylcellulose, hydroxypropyl ethyl cellulose, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, polyvinylacetatephthalates, phthalated gelatin, crosslinked gelatin, poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polycaprolactone and combinations thereof.
  - 86. The process of claim 84, wherein said polymer further comprises a polymer selected from the group consisting of methylmethacrylate copolymer, polyacrylic acid polymer, poly(glycolic acid) (PGA), poly(lactic acid) (PLA), poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polydioxanones, polyoxalates, poly({acute over (α
    - )}-esters), polyanhydrides, polyacetates, polycaprolactones, poly(orthoesters), polyamino acids, polyaminocarbonates, polyurethanes, polycarbonates, polyamides, poly(alkyl cyanoacrylates), and mixtures and copolymers thereof.
  - 87. The process of claim 84, wherein said polymer further comprises a polymer selected from the group consisting of sodium alginate, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, starch, gelatin, carageenan, locust bean gum, dextran, gellan gum and combinations thereof.
  - 88. The process of claim 84, wherein said polymer further comprises a polymer selected from the group consisting of ethylcellulose, hydroxypropyl ethyl cellulose, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, polyvinylacetatephthalates, phthalated gelatin, crosslinked gelatin, poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polycaprolactone, methylmethacrylate copolymer, polyacrylic acid polymer, poly(glycolic acid) (PGA), poly(lactic acid) (PLA), poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polydioxanones, polyoxalates, poly({acute over (α
    - )}-esters), polyanhydrides, polyacetates, polycaprolactones, poly(orthoesters), polyamino acids, polyaminocarbonates, polyurethanes, polycarbonates, polyamides, poly(alkyl cyanoacrylates), sodium alginate, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, starch, gelatin, carageenan, locust bean gum, dextran, gellan gum and combinations thereof.
  - 89. The process of claim 82, wherein said solvent is selected from the group consisting of water, polar organic solvent, and combinations thereof.
  - 90. The process of claim 89, wherein said solvent is selected from the group consisting of ethanol, isopropanol, acetone, and combinations thereof.
  - 91. The process of claim 82, wherein said active is selected from the group consisting of bioactive active, pharmaceutical actives, drugs, medicaments and combinations thereof.
  - 92. The process of claim 82, wherein the active is selected from the group consisting of ace-inhibitors, anti-anginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, analgesics, anesthetics, anti-convulsants, anti-depressants, anti-diabetic agents, anti-diarrhea preparations, antidotes, anti-histamines, anti-hypertensive drugs, anti-inflammatory agents, anti-lipid agents, anti-manics, anti-nauseants, anti-stroke agents, anti-thyroid preparations, anti-tumor drugs, anti-viral agents, acne drugs, alkaloids, amino acid preparations, anti-tussives, anti-uricemic drugs, anti-viral drugs, anabolic preparations, systemic and non-systemic anti-infective agents, anti-neoplastics, anti-parkinsonian agents, anti-rheumatic agents, appetite stimulants, blood modifiers, bone metabolism regulators, cardiovascular agents, central nervous system stimulates, cholinesterase inhibitors, contraceptives, decongestants, dietary supplements, dopamine receptor agonists, endometriosis management agents, enzymes, erectile dysfunction therapies, fertility agents, gastrointestinal agents, homeopathic remedies, hormones, hypercalcemia and hypocalcemia management agents, immunomodulators, immunosuppressives, migraine preparations, motion sickness treatments, muscle relaxants, obesity management agents, osteoporosis preparations, oxytocics, parasympatholytics, parasympathomimetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, smoking cessation aids, sympatholytics, tremor preparations, urinary tract agents, vasodilators, laxatives, antacids, ion exchange resins, anti-pyretics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, psycho-tropics, stimulants, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, anti-tumor drugs, anti-coagulants, anti-thrombotic drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo-glycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, uterine relaxants, anti-obesity drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof.
  - 93. The process of claim 82, wherein said active is selected from the group consisting of cosmetic actives, antigens, allergens, spores, microorganisms, seeds, mouthwash components, flavors, fragrances, enzymes, preservatives, sweetening agents, colorants, spices, vitamins and combinations thereof.
  - 94. The process of claim 82, wherein said active is a bioactive active.
  - 95. The process of claim 82, wherein said active is a biological response modifier.
  - 96. The process of claim 82, wherein said active is an opiate or opiate-derivative.
  - 97. The process of claim 82, wherein said active is an anti-emetic.
  - 98. The process of claim 82, wherein said active is an amino acid preparation.
  - 99. The process of claim 82, wherein said active is selected from the group consisting of sildenafils, tadalafils, vardenafils, apomorphines, yohimbine hydrochlorides, alprostadils and combinations thereof.
  - 100. The process of claim 82, wherein said active is a protein.
  - 101. The process of claim 82, wherein said active is insulin.
  - 102. The process of claim 82, wherein said active is an anti-diabetic.
  - 103. The process of claim 82, wherein said active is an antihistamine.
  - 104. The process of claim 82, wherein said active is an anti-tussive.
  - 105. The process of claim 82, wherein said active is a non-steroidal anti-inflammatory.
  - 106. The process of claim 82, wherein said active is an anti-asthmatics.
  - 107. The process of claim 82, wherein said active is an anti-diarrhea.
  - 108. The process of claim 82, wherein said active is an alkaloid.
  - 109. The process of claim 82, wherein said active is an anti-psychotic.
  - 110. The process of claim 82, wherein said active is an anti-spasmodic.
  - 111. The process of claim 82, wherein said active is a biological response modifier.
  - 112. The process of claim 82, wherein said active is an anti-obesity drug.
  - 113. The process of claim 82, wherein said active is an H₂-antagonist.
  - 114. The process of claim 82, wherein said H₂-antagonist is selected from the group consisting of cimetidine, ranitidine hydrochloride, famotidine, nizatidine, ebrotidine, mifentidine, roxatidine, pisatidine, aceroxatidine and combinations thereof.
  - 115. The process of claim 82, wherein said active is a smoking cessation aid.
  - 116. The process of claim 82, wherein said active is an anti-parkinsonian agent.
  - 117. The process of claim 82, wherein said active is an anti-depressant.
  - 118. The process of claim 82, wherein said active is an anti-migraine.
  - 119. The process of claim 82, wherein said active is an anti-Alzheimer'"'"'s agents.
  - 120. The process of claim 82, wherein said active is a dopamine receptor agonist.
  - 121. The process of claim 82, wherein said active is a cerebral dilator.
  - 122. The process of claim 82, wherein said active is a psychotherapeutic agent.
  - 123. The process of claim 82, wherein said active is an antibiotic.
  - 124. The process of claim 82, wherein said active is an anesthetic.
  - 125. The process of claim 82, wherein said active is a contraceptive.
  - 126. The process of claim, 82, wherein said active is an anti-thrombotic drug.
  - 127. The process of claim 82, wherein said active is diphenhydramine.
  - 128. The process of claim 82, wherein said active is nabilone.
  - 129. The process of claim 82, wherein said active is albuterol sulfate.
  - 130. The process of claim 82, wherein said active is an anti-tumor drug.
  - 131. The process of claim 82, wherein said active is a glycoprotein.
  - 132. The process of claim 82, wherein said active is an analgesic.
  - 133. The process of claim 82, wherein said active is a hormone.
  - 134. The process of claim 82, wherein said active is a decongestant.
  - 135. The process of claim 82, wherein said active is a loratadine.
  - 136. The process of claim 82, wherein said active is dextromethorphan.
  - 137. The process of claim 82, wherein said active is chlorpheniramine maleate.
  - 138. The process of claim 82, wherein said active is selected from the group consisting of an analgesic, an anti-inflammatory, an antihistamine, a decongestant, a cough suppressant and combinations thereof.
  - 139. The process of claim 82, wherein said active is an appetite stimulant.
  - 140. The process of claim 82, wherein said active is a gastrointestinal agent.
  - 141. The process of claim 82, wherein said active is a hypnotic.
  - 142. The process of claim 82, wherein said active is taste-masked.
  - 143. The process of claim 82, wherein said active is taste-masked using a flavor.
  - 144. The process of claim 82, wherein said active is coated with a controlled release composition.
  - 145. The process of claim 144, wherein said controlled release composition provides an immediate release.
  - 146. The process of claim 144, wherein said controlled release composition provides a delayed release.
  - 147. The process of claim 144, wherein said controlled release composition provides a sustained release.
  - 148. The process of claim 144, wherein said controlled release composition provides a sequential release.
  - 149. The process of claim 82, wherein said active is a particulate.
  - 150. The process of claim 82, further comprising adding a degassing agent to said flowable polymer matrix.
  - 151. The process of claim 82, further comprising a step of providing a second film layer.
  - 152. The process of claim 151, wherein said second film layer is coated onto said resulting film.
  - 153. The process of claim 151, wherein said second film layer is spread onto said resulting film.
  - 154. The process of claim 151, wherein said second film layer is cast onto said resulting film.
  - 155. The process of claim 151, wherein said second film layer is extruded onto said resulting film.
  - 156. The process of claim 151, wherein said second film layer is sprayed onto said resulting film.
  - 157. The process of claim 151, wherein said second film layer is laminated onto said resulting film.
  - 158. The process of claim 151, further comprising laminating said resulting film to another film.
  - 159. The process of claim 151, wherein said second film comprises an active.
  - 160. The process of claim 151, wherein said active in said second film is different than said active in said resulting film.
  - 261. The process of claim 82, said active is an anti-nauseant.
  - 262. The process of claim 82, said active is an erectile dysfunction.
  - 263. The process of claim 82, said active is a vasoconstrictor.
  - 264. The process of claim 82, said active is a stimulant.
  - 265. The process of claim 82, said active is a migraine treatment.
  - 266. The process of claim 82, said active is granisetron hydrochloride.
  - 267. The process of claim 82, wherein said resulting film provides administration of said active to an individual through the buccal cavity of said individual.
  - 268. The process of claim 82, wherein said resulting film provides administration of said active through gingival application of said individual.
  - 269. The process of claim 82, wherein said resulting film provides administration of said active through sublingual application of said individual.
  - 270. The process of claim 82, wherein said resulting film provides administration of said active to an individual through a mucosal membrane of said individual.
  - 271. The process of claim 82, wherein said resulting film provides administration of said active to an individual by administration within the body of the individual during surgery.
  - 272. The process of claim 82, wherein said resulting film has a variation of active content of less than 10% per film unit.
  - 273. The process of claim 82, further comprising the step of forming a plurality of individual dosage units of substantially the same size, wherein the active content of individual dosage units has a variance of no more than 10%.
  - 274. The method of claim 82, wherein said resulting film contains less than about 6% by weight solvent.
  - 275. The method of claim 82, wherein said at least one edible polymer, said active, and said at least one polar solvent are each ingestible materials.
  - 276. The method of claim 82, wherein said resulting film is orally administrable.
  - 277. The method of claim 82, wherein said active is in the form of a particle.
  - 278. The method of claim 82, wherein said matrix comprises a dispersion.
  - 298. The method of claim 82, wherein said matrix comprises an emulsion, a colloid or a suspension.

161. A process for making a film capable of being administered to a body surface having a substantially uniform distribution of components, comprising the steps of:
- (a) forming a flowable polymer matrix comprising a water-soluble polymer, a solvent and an active, said matrix having a substantially uniform distribution of said active;
  
  (b) casting said flowable polymer matrix;
  
  (c) evaporating at least a portion of said solvent from said flowable polymer matrix to form a visco-elastic film within about 10 minutes or fewer to maintain said substantially uniform distribution of said active by locking-in or substantially preventing migration of said active within said visco-elastic film;
  
  (d) forming a resulting film from said visco-elastic film, wherein said resulting film has a water content of 10% or less and said substantially uniform distribution of active by said locking-in or substantially preventing migration of said active is maintained; and
  
  (e) administering said resulting film to a body surface.
- View Dependent Claims (162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 299)
- - 162. The process of claim 161, wherein said body surface is a mucous membrane.
  - 163. The process of claim 162, wherein said mucous membrane is oral, anal, vaginal or ophthalmological.
  - 164. The process of claim 161, wherein said body surface is the surface of a wound.
  - 165. The process of claim 161, wherein said water-soluble polymer comprises polyethylene oxide.
  - 166. The process of claim 161, wherein said polymer comprises a polymer selected from the group consisting of cellulose, a cellulose derivative, pullulan, polyvinyl pyrrolidone, polyvinyl alcohol, polyethylene glycol, carboxyvinyl copolymers, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, sodium alginate, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, and combinations thereof, alone or in combination with polyethylene oxide.
  - 167. The process of claim 166, wherein said polymer further comprises a water insoluble polymer selected from the group consisting of ethylcellulose, hydroxypropyl ethyl cellulose, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, polyvinylacetatephthalates, phthalated gelatin, crosslinked gelatin, poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polycaprolactone and combinations thereof.
  - 168. The process of claim 166, wherein said polymer further comprises a polymer selected from the group consisting of methylmethacrylate copolymer, polyacrylic acid polymer, poly(glycolic acid) (PGA), poly(lactic acid) (PLA), poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polydioxanones, polyoxalates, poly({acute over (α
    - )}-esters), polyanhydrides, polyacetates, polycaprolactones, poly(orthoesters), polyamino acids, polyaminocarbonates, polyurethanes, polycarbonates, polyamides, poly(alkyl cyanoacrylates), and mixtures and copolymers thereof.
  - 169. The process of claim 166, wherein said polymer further comprises a polymer selected from the group consisting of sodium alginate, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, starch, gelatin, carageenan, locust bean gum, dextran, gellan gum and combinations thereof.
  - 170. The process of claim 166, wherein said polymer further comprises a polymer selected from the group consisting of ethylcellulose, hydroxypropyl ethyl cellulose, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, polyvinylacetatephthalates, phthalated gelatin, crosslinked gelatin, poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polycaprolactone, methylmethacrylate copolymer, polyacrylic acid polymer, poly(glycolic acid) (PGA), poly(lactic acid) (PLA), poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, polydioxanones, polyoxalates, poly({acute over (α
    - )}-esters), polyanhydrides, polyacetates, polycaprolactones, poly(orthoesters), polyamino acids, polyaminocarbonates, polyurethanes, polycarbonates, polyamides, poly(alkyl cyanoacrylates), sodium alginate, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, starch, gelatin, carageenan, locust bean gum, dextran, gellan gum and combinations thereof.
  - 171. The process of claim 161, wherein said solvent is selected from the group consisting of water, polar organic solvent, and combinations thereof.
  - 172. The process of claim 161, wherein said solvent is selected from the group consisting of ethanol, isopropanol, acetone, and combinations thereof.
  - 173. The process of claim 161, wherein said active is selected from the group consisting of bioactive active, pharmaceutical actives, drugs, medicaments and combinations thereof.
  - 174. The process of claim 161, wherein said active is selected from the group consisting of ace-inhibitors, anti-anginal drugs, anti-arrhythmias, anti-asthmatics, anti-cholesterolemics, analgesics, anesthetics, anti-convulsants, anti-depressants, anti-diabetic agents, anti-diarrhea preparations, antidotes, anti-histamines, anti-hypertensive drugs, anti-inflammatory agents, anti-lipid agents, anti-manics, anti-nauseants, anti-stroke agents, anti-thyroid preparations, anti-tumor drugs, anti-viral agents, acne drugs, alkaloids, amino acid preparations, anti-tussives, anti-uricemic drugs, anti-viral drugs, anabolic preparations, systemic and non-systemic anti-infective agents, anti-neoplastics, anti-parkinsonian agents, anti-rheumatic agents, appetite stimulants, blood modifiers, bone metabolism regulators, cardiovascular agents, central nervous system stimulates, cholinesterase inhibitors, contraceptives, decongestants, dietary supplements, dopamine receptor agonists, endometriosis management agents, enzymes, erectile dysfunction therapies, fertility agents, gastrointestinal agents, homeopathic remedies, hormones, hypercalcemia and hypocalcemia management agents, immunomodulators, immunosuppressives, migraine preparations, motion sickness treatments, muscle relaxants, obesity management agents, osteoporosis preparations, oxytocics, parasympatholytics, parasympathomimetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, smoking cessation aids, sympatholytics, tremor preparations, urinary tract agents, vasodilators, laxatives, antacids, ion exchange resins, anti-pyretics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, psycho-tropics, stimulants, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, anti-tumor drugs, anti-coagulants, anti-thrombotic drugs, hypnotics, anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo-glycemic agents, thyroid and anti-thyroid preparations, diuretics, anti-spasmodics, uterine relaxants, anti-obesity drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof.
  - 175. The process of claim 161, wherein said active is selected from the group consisting of cosmetic actives, antigens, allergens, spores, microorganisms, seeds, mouthwash components, flavors, fragrances, enzymes, preservatives, sweetening agents, colorants, spices, vitamins and combinations thereof.
  - 176. The process of claim 161, wherein said active is a bioactive active.
  - 177. The process of claim 161, wherein said active is a biological response modifier.
  - 178. The process of claim 161, wherein said active is an opiate or opiate-derivative.
  - 179. The process of claim 161, wherein said active is an anti-emetic.
  - 180. The process of claim 161 wherein said active is an amino acid preparation.
  - 181. The process of claim 161, wherein said active is selected from the group consisting of sildenafils, tadalafils, vardenafils, apomorphines, yohimbine hydrochlorides, alprostadils and combinations thereof.
  - 182. The process of claim 161, wherein said active is a protein.
  - 183. The process of claim 161, wherein said active is insulin.
  - 184. The process of claim 161, wherein said active is an anti-diabetic.
  - 185. The process of claim 161, wherein said active is an antihistamine.
  - 186. The process of claim 161, wherein said active is an anti-tussive.
  - 187. The process of claim 161, wherein said active is a non-steroidal anti-inflammatory.
  - 188. The process of claim 161, wherein said active is an anti-asthmatics.
  - 189. The process of claim 161, wherein said active is an anti-diarrhea.
  - 190. The process of claim 161, wherein said active is an alkaloid.
  - 191. The process of claim 161, wherein said active is an anti-psychotic.
  - 192. The process of claim 161, wherein said active is an anti-spasmodic.
  - 193. The process of claim 161, wherein said active is a biological response modifier.
  - 194. The process of claim 161, wherein said active is an anti-obesity drug.
  - 195. The process of claim 161, wherein said active is an H₂-antagonist.
  - 196. The process of claim 195, wherein said H₂-antagonist is selected from the group consisting of cimetidine, ranitidine hydrochloride, famotidine, nizatidine, ebrotidine, mifentidine, roxatidine, pisatidine, aceroxatidine and combinations thereof.
  - 197. The process of claim 161, wherein said active is a smoking cessation aid.
  - 198. The process of claim 161, wherein said active is an anti-parkinsonian agent.
  - 199. The process of claim 161, wherein said active is an anti-depressant.
  - 200. The process of claim 161, wherein said active is an anti-migraine.
  - 201. The process of claim 161, wherein said active is an anti-Alzheimer'"'"'s agents.
  - 202. The process of claim 161, wherein said active is a dopamine receptor agonist.
  - 203. The process of claim 161, wherein said active is a cerebral dilator.
  - 204. The process of claim 161, wherein said active is a psychotherapeutic agent.
  - 205. The process of claim 161, wherein said active is an antibiotic.
  - 206. The process of claim 161, wherein said active is an anesthetic.
  - 207. The process of claim 161, wherein said active is a contraceptive.
  - 208. The process of claim 161, wherein said active is an anti-thrombotic drug.
  - 209. The process of claim 161, wherein said active is diphenhydramine.
  - 210. The process of claim 161, wherein said active is nabilone.
  - 211. The process of claim 161, wherein said active is albuterol sulfate.
  - 212. The process of claim 161, wherein said active is an anti-tumor drug.
  - 213. The process of claim 161, wherein said active is a glycoprotein.
  - 214. The process of claim 161, wherein said active is an analgesic.
  - 215. The process of claim 161, wherein said active is a hormone.
  - 216. The process of claim 161, wherein said active is a decongestant.
  - 217. The process of claim 161, wherein said active is a loratadine.
  - 218. The process of claim 161, wherein said active is dextromethorphan.
  - 219. The process of claim 161, wherein said active is chlorpheniramine maleate.
  - 220. The process of claim 161, wherein said active is selected from the group consisting of an analgesic, an anti-inflammatory, an antihistamine, a decongestant, a cough suppressant and combinations thereof.
  - 221. The process of claim 161, wherein said active is an appetite stimulant.
  - 222. The process of claim 161, wherein said active is a gastrointestinal agent.
  - 223. The process of claim 161, wherein said active is a hypnotic.
  - 224. The process of claim 161, wherein said active is taste-masked.
  - 225. The process of claim 161, wherein said active is taste-masked using a flavor.
  - 226. The process of claim 161, wherein said active is coated with a controlled release composition.
  - 227. The process of claim 226, wherein said controlled release composition provides an immediate release.
  - 229. The process of claim 226, wherein said controlled release composition provides a sustained release.
  - 230. The process of claim 226, wherein said controlled release composition provides a sequential release.
  - 231. The process of claim 161, wherein said active is a particulate.
  - 232. The process of claim 161, further comprising adding a degassing agent to said flowable polymer matrix.
  - 233. The process of claim 161, further comprising a step of providing a second film layer.
  - 234. The process of claim 233, wherein said second film layer is coated onto said resulting film.
  - 235. The process of claim 233, wherein said second film layer is spread onto said resulting film.
  - 236. The process of claim 233, wherein said second film layer is cast onto said resulting film.
  - 237. The process of claim 233, wherein said second film layer is extruded onto said resulting film.
  - 238. The process of claim 233, wherein said second film layer is sprayed onto said resulting film.
  - 239. The process of claim 233, wherein said second film layer is laminated onto said resulting film.
  - 240. The process of claim 233, further comprising laminating said resulting film to another film.
  - 241. The process of claim 233, wherein said second film comprises an active.
  - 242. The process of claim 233, wherein said active in said second film is different than said active in said resulting film.
  - 279. The process of claim 161, said active is an anti-nauseant.
  - 280. The process of claim 161, said active is an erectile dysfunction.
  - 281. The process of claim 161, said active is a vasoconstrictor.
  - 282. The process of claim 161, said active is a stimulant.
  - 283. The process of claim 161, said active is a migraine treatment.
  - 284. The process of claim 161, said active is granisetron hydrochloride.
  - 285. The process of claim 161, wherein said resulting film provides administration of said active to an individual through the buccal cavity of said individual.
  - 286. The process of claim 161, wherein said resulting film provides administration of said active through gingival application of said individual.
  - 287. The process of claim 161, wherein said resulting film provides administration of said active through sublingual application of said individual.
  - 288. The process of claim 161, wherein said resulting film provides administration of said active to an individual through a mucosal membrane of said individual.
  - 289. The process of claim 161, wherein said resulting film provides administration of said active to an individual by administration within the body of the individual during surgery.
  - 290. The process of claim 161, wherein said resulting film has a variation of active content of less than 10% per film unit.
  - 291. The process of claim 161, further comprising the step of forming a plurality of individual dosage units of substantially the same size, wherein the active content of individual dosage units has a variance of no more than 10%.
  - 292. The method of claim 161, wherein said resulting film contains less than about 6% by weight solvent.
  - 293. The method of claim 161, wherein said at least one edible polymer, said active, and said at least one polar solvent are each ingestible materials.
  - 294. The method of claim 161, wherein said resulting film is orally administrable.
  - 295. The method of claim 161, wherein said active is in the form of a particle.
  - 296. The method of claim 161, wherein said matrix comprises a dispersion.
  - 299. The method of claim 161, wherein said matrix comprises an emulsion, a colloid or a suspension.

228. The process of 226, wherein said controlled release composition provides a delayed release.

Specification

Resources

Litigation Campaign Assessment

Litigation Data

Current Assignee
Monosol Rx LLC (Kuraray Company Limited)
Original Assignee
Monosol Rx LLC (Kuraray Company Limited)
Inventors
Yang, Robert K., Fuisz, Joseph M., Fuisz, Richard C., Myers, Gary L.
Primary Examiner(s)
Lee; Edmund H.

Application Number

US12/614,928
Publication Number

US 20100092545A1
Time in Patent Office

477 Days
Field of Search

None
US Class Current

264/172.19
CPC Class Codes

A61K 2800/92   Oral administration

A61K 8/0216   Solid or semisolid forms

A61K 8/731   Cellulose; Quaternized cell...

A61K 8/86   Polyethers

A61K 9/006   Oral mucosa, e.g. mucoadhes...

A61K 9/7007   Drug-containing films, memb...

A61K 9/7015   Drug-containing film-formin...

A61P 1/12   Antidiarrhoeals

A61P 13/02   of urine or of the urinary ...

A61P 19/10   for osteoporosis

A61P 25/06   Antimigraine agents

A61P 25/18   Antipsychotics, i.e. neurol...

A61P 25/24   Antidepressants

A61P 25/28   for treating neurodegenerat...

A61P 25/34   Tobacco-abuse

A61P 29/00   Non-central analgesic, anti...

A61P 3/00   Drugs for disorders of the ...

A61P 3/10   for hyperglycaemia, e.g. an...

A61P 35/04   specific for metastasis

A61P 9/12   Antihypertensives

A61Q 11/00 : Preparations for care of th...

C08J 2371/02 : Polyalkylene oxides

C08J 5/18 : Manufacture of films or sheets

F26B 13/104 : supported by fluid jets onl...

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Polyethylene-oxide based films and drug delivery systems made therefrom

First Claim

4 Assignments

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Reexamination

Accused Products

Abstract

87 Citations

299 Claims

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Polyethylene-oxide based films and drug delivery systems made therefrom

First Claim

4 Assignments

Subscription Required

Subscription Required

Litigations

0 Petitions

Subscription Required

Reexamination

Accused Products

Subscription Required

Abstract

87 Citations

299 Claims

Specification

Subscription Required

Solutions

Use Cases

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