Claims for Patent: 8,603,514

Summary for Patent: 8,603,514

Title:	Uniform films for rapid dissolve dosage form incorporating taste-masking compositions
Abstract:	The present invention relates to rapid dissolve thin film drug delivery compositions for the oral administration of active components. The active components are provided as taste-masked or controlled-release coated particles uniformly distributed throughout the film composition. The compositions may be formed by wet casting methods, where the film is cast and controllably dried, or alternatively by an extrusion method.
Inventor(s):	Yang; Robert K. (Fushing, NY), Fuisz; Richard C. (McLean, VA), Myers; Garry L. (Kingsport, TN), Fuisz; Joseph M. (Washington, DC)
Assignee:	MonoSol RX, LLC (Warren, NJ)
Application Number:	11/775,484
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,603,514
Patent Claims:	1. A drug delivery composition comprising: (i) a cast film comprising a flowable water-soluble or water swellable film-forming matrix comprising one or more substantially water soluble or water swellable polymers; and a desired amount of at least one active; wherein said matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the active in the matrix; (ii) a particulate active substantially uniformly stationed in the matrix; and (iii) a taste-masking agent coated or intimately associated with said particulate to provide taste-masking of the active; wherein the combined particulate and taste-masking agent have a particle size of 200 microns or less and said flowable water-soluble or water swellable film-forming matrix is capable of being dried without loss of substantial uniformity in the stationing of said particulate active therein; and wherein the uniformity subsequent to casting and drying of the matrix is measured by substantially equally sized individual unit doses which do not vary by more than 10% of said desired amount of said at least one active. 2. The drug delivery composition of claim 1, wherein the size of said combined particulate and taste-masking agent have a particle size of 150 microns or less. 3. The drug delivery composition of claim 1, wherein the size of said combined particulate and taste-masking agent have a particle size of 100 microns or less. 4. The drug delivery composition of claim 1, wherein said taste-masking agent is a thin film coating over portions of said active. 5. The drug delivery composition of claim 1, wherein the taste-masking agent is a polymer. 6. The drug delivery composition of claim 1, wherein the taste-masking agent is a water-soluble polymer. 7. The drug delivery composition of claim 6, wherein said water-soluble polymer has an average molecular weight of equal to or greater than about 40,000. 8. The drug delivery composition of claim 1, wherein the taste-masking agent is selected from the group consisting of acrylic polymers, cellulosic polymers, vinyl polymers, crown ethers, hydrogenated oils and waxes, and combinations thereof. 9. The drug delivery composition of claim 1, wherein said variation of drug content is less than 5% by weight per film dosage unit. 10. The drug delivery composition of claim 1, wherein said variation of drug content is less than 2% by weight per film dosage unit. 11. The drug delivery composition of claim 1, wherein said variation of drug content is less than 0.5% by weight per film dosage unit. 12. The drug delivery composition of claim 1, wherein said taste-masking agent is present in the amount of about 15-80% by weight of the particle. 13. The drug delivery composition of claim 1, wherein said taste-masking agent is present in the amount of about 20-60% by weight of the particle. 14. The drug delivery composition of claim 1, wherein said taste-masking agent is present in the amount of about 25-35% by weight of the particle. 15. The drug delivery composition of claim 1, wherein said active is selected from the group consisting of antimicrobial agents, non-steroidal anti-inflammatory drugs, anti-tussives, decongestants, antihistamines, expectorants, anti-diarrheals, H.sub.2 antagonists, proton pump inhibitors, general non-selective CNS depressants, general non-selective CNS stimulants, selective CNS functional modifiers, anti-parkinsonism drugs, narcotics, analgesics, erectile dysfunction therapies, anti-pyretics, psychopharmacological drugs and combinations thereof. 16. A thin film drug delivery composition comprising: (a) a cast film comprising an edible water-soluble or water swellable film-forming matrix comprising at least one water-soluble or water swellable polymer comprising polyethylene oxide alone or in combination with a hydrophilic cellulosic polymer; and a desired amount of at least one active; wherein said matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the active in the matrix; and (b) a coated particulate active component substantially uniformly stationed in the matrix; wherein the coating on the particulate active component is a taste-masking agent, and wherein the active component is substantially uniformly distributed in the film composition; and wherein the uniformity subsequent to casting and drying of the matrix is measured by substantially equally sized individual unit doses which do not vary by more than 10% of said desired amount of said at least one active. 17. The drug delivery composition of claim 16, wherein said thin film drug delivery composition is extruded. 18. The drug delivery composition of claim 16, wherein the taste-masking agent is a thin film coating over the particulate active component. 19. The drug delivery composition of claim 16, wherein the taste-masking agent is a water-soluble polymer. 20. The drug delivery composition of claim 16, wherein the composition is free of added plasticizers, surfactants, or polyalcohols. 21. The drug delivery composition of claim 1, wherein the taste-masking agent is selected from the group consisting of carboxymethyl cellulose; methyl cellulose; ethyl cellulose; hydroxyl methyl cellulose; hydroxyethyl cellulose; hydroxypropyl cellulose; hydroxypropylmethyl cellulose; hydroxymethylpropyl cellulose; gum arabic; xanthan gum; tragacanth; acacia; carageenan; guar gum; locust bean gum; pectin; alginates; gelatinized, modified or unmodified starch; polyvinyl alcohol; polyacrylic acid; polyvinyl pyrrolidone; poly(meth)acrylate; poly(meth)copolymers; dextrin; dextran; proteins; whey protein isolate; casein; levin; collagen; chitin; chitosin; polydextrose and combinations thereof. 22. The drug delivery composition of claim 1, wherein said active is selected from the group consisting of ace-inhibitors, antianginal 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, biological response modifiers, 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, terine relaxants, anti-obesity drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof. 23. The drug delivery composition of claim 1, wherein the film forming matrix has the viscosity in an amount sufficient to substantially prevent an active from settling out during mixing or coating. 24. The drug delivery composition of claim 1, wherein said taste-masking agent is selected from the group consisting of flavors, sweeteners, flavor enhancers, and combinations thereof. 25. The drug delivery composition of claim 1, wherein said active is an opiate or opiate derivative. 26. The drug delivery composition of claim 16, wherein said taste-masking agent is selected from the group consisting of flavors, sweeteners, flavor enhancers, and combinations thereof. 27. The drug delivery composition of claim 16, wherein said active is an opiate or opiate derivative. 28. A drug delivery composition comprising: (i) a cast film comprising a flowable water-soluble or water swellable film-forming matrix comprising one or more substantially water soluble or water swellable polymers; and a desired amount of at least one active; wherein said matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the active in the matrix; (ii) a particulate active substantially uniformly stationed in the matrix; and (iii) a taste-masking agent coated or intimately associated with said particulate to provide taste-masking of the active; wherein the combined particulate and taste-masking agent have a particle size of 200 microns or less and said flowable water-soluble or water swellable film-forming matrix is capable of being dried without loss of substantial uniformity in the stationing of said particulate active therein; wherein the uniformity subsequent to casting and drying of the matrix is measured by substantially equally sized individual unit doses which do not vary by more than 10% of said desired amount of said at least one active; and wherein the coated particulate active has a shape selected from the group consisting of spherically shaped particles, ellipsoidally shaped particles, irregularly shaped particles, and combinations thereof. 29. The drug delivery composition of claim 28, wherein the size of said combined particulate and taste-masking agent have a particle size of 150 microns or less. 30. The drug delivery composition of claim 28, wherein the size of said combined particulate and taste-masking agent have a particle size of 100 microns or less. 31. The drug delivery composition of claim 28, wherein said taste-masking agent is a thin film coating over portions of said active. 32. The drug delivery composition of claim 28, wherein the taste-masking agent is a polymer. 33. The drug delivery composition of claim 28, wherein the taste-masking agent is a water-soluble polymer. 34. The drug delivery composition of claim 33, wherein said water-soluble polymer has an average molecular weight of equal to or greater than about 40,000. 35. The drug delivery composition of claim 28, wherein the taste-masking agent is selected from the group consisting of acrylic polymers, cellulosic polymers, vinyl polymers, crown ethers, hydrogenated oils and waxes, and combinations thereof. 36. The drug delivery composition of claim 28, wherein said variation of drug content is less than 5% by weight per film dosage unit. 37. The drug delivery composition of claim 28, wherein said variation of drug content is less than 2% by weight per film dosage unit. 38. The drug delivery composition of claim 28, wherein said variation of drug content is less than 0.5% by weight per film dosage unit. 39. The drug delivery composition of claim 28, wherein said taste-masking agent is present in the amount of about 15-80% by weight of the particle. 40. The drug delivery composition of claim 28, wherein said taste-masking agent is present in the amount of about 20-60% by weight of the particle. 41. The drug delivery composition of claim 28, wherein said taste-masking agent is present in the amount of about 25-35% by weight of the particle. 42. The drug delivery composition of claim 28, wherein said active is selected from the group consisting of antimicrobial agents, non-steroidal anti-inflammatory drugs, anti-tussives, decongestants, antihistamines, expectorants, anti-diarrheals, H.sub.2 antagonists, proton pump inhibitors, general non-selective CNS depressants, general non-selective CNS stimulants, selective CNS functional modifiers, anti-parkinsonism drugs, narcotics, analgesics, erectile dysfunction therapies, anti-pyretics, psychopharmacological drugs and combinations thereof. 43. The drug delivery composition of claim 28, wherein the taste-masking agent is selected from the group consisting of carboxymethyl cellulose; methyl cellulose; ethyl cellulose; hydroxyl methyl cellulose; hydroxyethyl cellulose; hydroxypropyl cellulose; hydroxypropylmethyl cellulose; hydroxymethylpropyl cellulose; gum arabic; xanthan gum; tragacanth; acacia; carageenan; guar gum; locust bean gum; pectin; alginates; gelatinized, modified or unmodified starch; polyvinyl alcohol; polyacrylic acid; polyvinyl pyrrolidone; poly(meth)acrylate; poly(meth)copolymers; dextrin; dextran; proteins; whey protein isolate; casein; levin; collagen; chitin; chitosin; polydextrose and combinations thereof. 44. The drug delivery composition of claim 28, wherein said active is selected from the group consisting of ace-inhibitors, antianginal 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, biological response modifiers, 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, terine relaxants, anti-obesity drugs, erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics, DNA and genetic modifying drugs, and combinations thereof. 45. The drug delivery composition of claim 28, wherein the film forming matrix has the viscosity in an amount sufficient to substantially prevent an active from settling out during mixing or coating. 46. The drug delivery composition of claim 28, wherein said taste-masking agent is selected from the group consisting of flavors, sweeteners, flavor enhancers, and combinations thereof. 47. The drug delivery composition of claim 28, wherein said active is an opiate or opiate derivative. 48. A thin film drug delivery composition comprising: (a) a cast film comprising an edible water-soluble or water swellable film-forming matrix comprising at least one water-soluble or water swellable polymer comprising polyethylene oxide alone or in combination with a hydrophilic cellulosic polymer; and a desired amount of at least one active; wherein said matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the active in the matrix; and (b) a coated particulate active component substantially uniformly stationed in the matrix; wherein the coating on the particulate active component is a taste-masking agent, and wherein the active component is substantially uniformly distributed in the film composition; wherein the uniformity subsequent to casting and drying of the matrix is measured by substantially equally sized individual unit doses which do not vary by more than 10% of said desired amount of said at least one active; and wherein the at least one water-soluble polymer comprises about 20% to about 100% by weight polyethylene oxide. 49. The drug delivery composition of claim 48, wherein said thin film drug delivery composition is extruded. 50. The drug delivery composition of claim 48, wherein the taste-masking agent is a thin film coating over the particulate active component. 51. The drug delivery composition of claim 48, wherein the taste-masking agent is a water-soluble polymer. 52. The drug delivery composition of claim 48, wherein the composition is free of added plasticizers, surfactants, or polyalcohols. 53. The drug delivery composition of claim 48, wherein said taste-masking agent is selected from the group consisting of flavors, sweeteners, flavor enhancers, and combinations thereof. 54. The drug delivery composition of claim 48, wherein said active is an opiate or opiate derivative. 55. A thin film drug delivery composition comprising: (a) a cast film comprising an edible water-soluble or water swellable film-forming matrix comprising at least one water-soluble or water swellable polymer comprising polyethylene oxide alone or in combination with a hydrophilic cellulosic polymer; and a desired amount of at least one active; wherein said matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the active in the matrix; and (b) a coated particulate active component substantially uniformly stationed in the matrix; wherein the coating on the particulate active component is a taste-masking agent, and wherein the active component is substantially uniformly distributed in the film composition; wherein the uniformity subsequent to casting and drying of the matrix is measured by substantially equally sized individual unit doses which do not vary by more than 10% of said desired amount of said at least one active; and wherein the at least one water-soluble polymer comprises a hydrophilic cellulosic polymer in a ratio of up to about 4:1 with polyethylene oxide. 56. The drug delivery composition of claim 55, wherein said thin film drug delivery composition is extruded. 57. The drug delivery composition of claim 55, wherein the taste-masking agent is a thin film coating over the particulate active component. 58. The drug delivery composition of claim 55, wherein the taste-masking agent is a water-soluble polymer. 59. The drug delivery composition of claim 55, wherein the composition is free of added plasticizers, surfactants, or polyalcohols. 60. The drug delivery composition of claim 55, wherein said taste-masking agent is selected from the group consisting of flavors, sweeteners, flavor enhancers, and combinations thereof. 61. The drug delivery composition of claim 55, wherein said active is an opiate or opiate derivative. 62. A drug delivery composition comprising: (i) a cast film comprising a flowable water-soluble or water swellable film-forming matrix comprising one or more substantially water soluble or water swellable polymers; and a desired amount of at least one active; wherein said matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the active in the matrix; (ii) a particulate active substantially uniformly stationed in the matrix; and (iii) a taste-masking agent selected from the group consisting of flavors, sweeteners, flavor enhancers, and combinations thereof to provide taste-masking of the active; wherein the particulate active has a particle size of 200 microns or less and said flowable water-soluble or water swellable film-forming matrix is capable of being dried without loss of substantial uniformity in the stationing of said particulate active therein; and wherein the uniformity subsequent to casting and drying of the matrix is measured by substantially equally sized individual unit doses which do not vary by more than 10% of said desired amount of said at least one active. 63. The drug delivery composition of claim 62, wherein the particulate active has a particle size of 150 microns or less. 64. The drug delivery composition of claim 62, wherein the particulate active has a particle size of 100 microns or less. 65. The drug delivery composition of claim 62, wherein said variation of drug content is less than 5% by weight per film dosage unit. 66. The drug delivery composition of claim 62, wherein said variation of drug content is less than 2% by weight per film dosage unit. 67. The drug delivery composition of claim 62, wherein said variation of drug content is less than 0.5% by weight per film dosage unit. 68. The drug delivery composition of claim 62, wherein the particulate active has a shape selected from the group consisting of spherically shaped particles, ellipsoidally shaped particles, irregularly shaped particles, and combinations thereof. 69. The drug delivery composition of claim 62, wherein said taste-masking agent is present in the amount of about 0.1-30% by weight of the drug delivery composition. 70. The drug delivery composition of claim 62, wherein said taste-masking agent is present in the amount of about 0.01-10% by weight of the drug delivery composition. 71. The drug delivery composition of claim 62, wherein said active is selected from the group consisting of antimicrobial agents, non-steroidal anti-inflammatory drugs, anti-tussives, decongestants, antihistamines, expectorants, anti-diarrheals, H.sub.2 antagonists, proton pump inhibitors, general non-selective CNS depressants, general non-selective CNS stimulants, selective CNS functional modifiers, anti-parkinsonism drugs, narcotics, analgesics, erectile dysfunction therapies, anti-pyretics, psychopharmacological drugs and combinations thereof. 72. The drug delivery composition of claim 62, wherein the film forming matrix has the viscosity in an amount sufficient to substantially prevent an active from settling out during mixing or coating. 73. The drug delivery composition of claim 62, wherein said active is an opiate or opiate derivative. 74. The drug delivery composition of claim 73, wherein said taste masking agent is peppermint oil. 75. The drug delivery composition of claim 1, wherein said active is an opiate or opiate derivative and said taste masking agent is selected from the group consisting of flavors, sweeteners, flavor enhancers, and combinations thereof. 76. The drug delivery composition of claim 75, wherein said taste masking agent is peppermint oil.