Uniform films for rapid dissolve dosage form incorporating taste-masking compositions

• US 8,603,514 B2
• Filed: 07/10/2007
• Issued: 12/10/2013
• Est. Priority Date: 04/11/2002
• Status: Expired due to Term

• Current Assignee: Aquestive Therapeutics, Inc.
• Original Assignee: Monosol Rx LLC (Kuraray Company Limited)
• Inventors: Fuisz, Richard C., Myers, Garry L., Fuisz, Joseph M., Yang, Robert K.
• Primary Examiner(s): Desai, Anand
• Assistant Examiner(s): MERCIER, MELISSA S
• Application Number:
  US11/775,484
• Publication Number:
  US 20080044454A1
• Time in Patent Office: 2,345 Days
• Field of Search: None
• US Class Current: 424/435
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 31/443 containing a five-membered ring with oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/549 having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• CPC Class Codes: A61K 31/635 having a heterocyclic ring, e.g. sulfadiazine
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/44 : Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 47/46 : Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
• CPC Class Codes: A61K 9/0056 : Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/006 : Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/14 : Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/501 : Inorganic compounds
• CPC Class Codes: A61K 9/5015 : Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5026 : obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5036 : Polysaccharides, e.g. gums, alginate; Cyclodextrin
• CPC Class Codes: A61K 9/5047 : Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/7007 : Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61K 9/7015 : Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: B05D 3/0254 : After-treatment
• CPC Class Codes: B29C 48/022 : characterised by the choice of material

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.

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, H₂ 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.

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.

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.

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.

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, H₂ 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, H₂ 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.