Rapidly dissolving film for delivery of an active agent

• US 8,658,201 B2
• Filed: 01/31/2005
• Issued: 02/25/2014
• Est. Priority Date: 01/30/2004
• Status: Active Grant

• Current Assignee: A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences,, Corium Pharma Solutions, Inc.
• Original Assignee: A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences,, Corium International, Inc.
• Inventors: Singh, Parminder, Mudumba, Sri, Bairamov, Danir R., Kulichikhin, Valery G., Feldstein, Mikhail M., Cleary, Gary W.
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): YOUNG, MICAH PAUL
• Application Number:
  US11/047,964
• Publication Number:
  US 20050208110A1
• Time in Patent Office: 3,312 Days
• Field of Search: 424/449, 424/435, 424/466, 424/439, 424/401, 424/426, 424/434, 424/443, 424/444
• US Class Current: 424/444
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• 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 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence

Abstract

A rapidly dissolving film is provided for delivery of an active agent to a moist body surface, e.g., mucosal tissue. The film comprises a film-forming binder, a rapidly dissolving polymeric material, and an active agent.

Claims

1. A film for administration of an active agent to a body surface, the film comprising:

a blend comprised of 30-70 wt % of a hydrophilic polymer and 10-40 wt % of a plasticizer miscible with the hydrophilic polymer, the hydrophilic polymer and the plasticizer blended to form non-covalent bonds between the hydrophilic polymer and the plasticizer, wherein the wt % of the hydrophilic polymer and plasticizer are based on the film composition exclusive of the active agent,

a rapidly dissolving polymeric material; and

an effective amount of an active agent,

wherein the blend and the rapidly dissolving material are effective to facilitate dissolution of the film within 10 minutes following application of the film to a moist body surface.

2. The film of claim 1, wherein the hydrophilic polymer comprises repeating units derived from monomers selected from N-vinyl lactam monomers, carboxy vinyl monomers, vinyl ester monomers, esters of a carboxy vinyl monomer, vinyl amide monomers, hydroxy vinyl monomers, and combinations thereof.

3. The film of claim 1, wherein the hydrophilic polymer is selected from poly(N-vinyl lactams), poly(N-vinyl amides), poly(N-vinyl acrylamides), poly(N-alkylacrylamides), poly(N-vinyl acetamides), substituted and unsubstituted acrylic and methacrylic acid polymers, polyvinyl alcohol, polyvinylamine, and copolymers and blends thereof.

4. The film of claim 3, wherein the hydrophilic polymer is selected from poly(N-vinyl lactams), poly(N-vinyl amides), poly(N-alkylacrylamides), and copolymers and blends thereof.

5. The film of claim 4, wherein the hydrophilic polymer is a poly(N-vinyl lactam).

6. The film of claim 5, wherein the hydrophilic polymer is a poly(N-vinyl lactam) homopolymer.

7. The film of claim 6, wherein the poly(N-vinyl lactam) is selected from polyvinyl pyrrolidone, polyvinyl caprolactam, and blends thereof.

8. The film of claim 7, wherein the poly(N-vinyl lactam) is polyvinyl pyrrolidone.

9. The film of claim 7, wherein the poly(N-vinyl lactam) is polyvinyl caprolactam.

10. The film of claim 3, wherein the hydrophilic polymer has a number average molecular weight in the range of approximately 100,000 to 2,000,000.

11. The film of claim 10, wherein the hydrophilic polymer has a number average molecular weight in the range of approximately 500,000 to 1,500,000.

12. The film of claim 1, wherein the plasticizer is selected from dialkyl phthalates, dicycloalkyl phthalates, diaryl phthalates, mixed alkyl-aryl phthalates, alkyl phosphates, aryl phosphates, alkyl citrates, citrate esters, alkyl adipates, dialkyl tartrates, dialkyl sebacates, dialkyl succinates, alkyl glycolates, alkyl glycerolates, glycol esters, glycerol esters, and mixtures thereof.

13. The film of claim 12, wherein the plasticizer is selected from dimethyl phthalate, diethyl phthalate, dipropyl phthalate, di(2-ethylhexyl)phthalate, di-isopropyl phthalate, diamyl phthalate, dicapryl phthalate, tributyl phosphate, trioctyl phosphate, tricresyl phosphate, triphenyl phosphate, trimethyl citrate, triethyl citrate, tributyl citrate, acetyl triethyl citrate, trihexyl citrate, dioctyl adipate, diethyl adipate, di(2-methylethyl)adipate, dihexyladipate, diethyl tartrate, dibutyl tartrate, diethyl sebacate, dipropyl sebacate, dinonyl sebacate, diethyl succinate, dibutyl succinate, glycerol diacetate, glycerol triacetate, glycerol mono lactate diacetate, methyl phthalyl ethyl glycolate, butyl phthalyl butyl glycolate, ethylene glycol diacetate, ethylene glycol dibutyrate, triethylene glycol diacetate, triethylene glycol dibutyrate, triethylene glycol dipropionate, and mixtures thereof.

14. The film of claim 13, wherein the plasticizer is selected from tributyl phosphate, trioctyl phosphate, triphenyl phosphate, trimethyl citrate, triethyl citrate, and tributyl citrate.

15. The film of claim 1, wherein the plasticizer is a bifunctional, linear oligomer having a functional group at each terminus, each of said terminal functional groups capable of non covalently binding to the hydrophilic polymer.

16. The film of claim 15, wherein the bifunctional, linear oligomer has a molecular weight in the range of approximately 45 to approximately 800 g/mol.

17. The film of claim 16, wherein the bifunctional, linear oligomer has a molecular weight in the range of approximately 45 to approximately 600 g/mol.

18. The film of claim 17, wherein the terminal functional groups are selected from hydroxyl, carboxy, and amino groups.

19. The film of claim 18, wherein the terminal functional groups are selected from hydroxyl and carboxy groups.

20. The film of claim 19, wherein the terminal functional groups are hydroxyl groups.

21. The film of claim 20, wherein the weight ratio of the hydrophilic polymer to the plasticizer is in the range of about 1:

10 to about 10;

1.

22. The film of claim 21, wherein the weight ratio of the hydrophilic polymer to the plasticizer is about 1.5:

1 to about 3;

1.

23. The film of claim 22, wherein the weight ratio of hydrophilic polymer to complementary oligomer is about 2:

1.

24. The film of claim 15, wherein the bifunctional, linear oligomer has a molecular weight in the range of approximately 45 to approximately 800 g/mol.

25. The film of claim 24, wherein the bifunctional, linear oligomer has a molecular weight in the range of approximately 45 to approximately 600 g/mol.

26. The film of claim 25, wherein the terminal functional groups are selected from hydroxyl, carboxy, and amino groups.

27. The film of claim 26, wherein the terminal functional groups are selected from hydroxyl and carboxy groups.

28. The film of claim 27, wherein the terminal functional groups are hydroxyl groups.

29. The film of claim 1, wherein the weight ratio of the hydrophilic polymer to the plasticizer is in the range of about 1:

10 to about 10;

1.

30. The film of claim 29, wherein the weight ratio of the hydrophilic polymer to the plasticizer is about 1.5:

1 to about 3;

1.

31. The film of claim 30, wherein the weight ratio of hydrophilic polymer to plasticizer is about 2:

1.

32. The film of claim 1, wherein the rapidly dissolving polymeric material is selected from oligosaccharides, polysaccharides, crosslinked polyvinylpyrrolidone, alginic acid, agar, and bentonite.

33. The film of claim 32, wherein the rapidly dissolving polymeric material is selected from oligosaccharides and polysaccharides.

34. The film of claim 33, wherein the rapidly dissolving polymeric material is selected from cellulose derivatives having a molecular weight in the range of about 1,000 to 300,000.

35. The film of claim 34, wherein the rapidly dissolving polymeric material is maltodextrin.

36. The film of claim 1, wherein the active agent is a pharmacologically active agent and the effective amount is a therapeutically effective amount.

37. The film of claim 36, wherein the active agent is a locally acting agent.

38. The film of claim 36, wherein the active agent is a systemically acting agent.

39. The film of claim 36, wherein the therapeutically effective amount is at most 300 mg/cm².

40. The film of claim 39, wherein the therapeutically effective amount is in the range of about 100 μ

g/cm² to 200 mg/cm².

41. The film of claim 40, wherein the therapeutically effective amount is in the range of about 1 mg/cm² to 100 mg/cm².

42. The film of claim 1, wherein the active agent is noncovalently bound to the hydrophilic polymer.

43. The film of claim 42, wherein the active agent is bound to the hydrophilic polymer via hydrogen bonds.

44. The film of claim 1, wherein the active agent is contained in discrete particles dispersed throughout the film.

45. The film of claim 1, which dissolves within about 5 to 30 seconds following application of the film to a moist body surface.

46. The film of claim 1, which dissolves in less than about 30 seconds following application of the film to a moist body surface.

47. The film of claim 1, having a thickness of at least one 1 mm.

48. The film of claim 47, having a thickness in the range of about 100 mm to 200 mm.

49. The film of claim 1, further comprising at least one additive selected from fillers, softeners, detackifiers, antioxidants, antimicrobial agents, preservatives, pH-regulating agents, and colorants.

50. The film of claim 1, wherein the at least one additive includes a softener.

51. The film of claim 50, wherein the softener is a hydrophilic surfactant.

52. A method for administering an active agent to a patient, comprising placing the film of claim 1 on a moist body surface of the patient and allowing the film to dissolve.

53. The method of claim 52, wherein the moist body surface of the patient is mucosal tissue.

54. The method of claim 53, wherein the moist body surface is selected from skin and integument that is externally moisturized.

62. The film of claim 1, comprising 10-40% of the rapidly dissolving polymeric material.

63. The film of claim 1, wherein the bifunctional, linear oligomer is polyethylene glycol.

64. The film of claim 52, wherein the polyethylene glycol has a molecular weight of 400.

55. A film for administration of an active agent to a body surface, the film comprising:

(a) a blend consisting of (i) 30-70 wt % of a hydrophilic polymer, and (ii) 10-40 wt % of an oligomer having a molecular weight of between 45 to 800 g/mol, and (b) 10-40 wt % of a rapidly dissolving polymeric material, the hydrophilic polymer and the oligomer blended to form non-covalent bonds between the hydrophilic polymer and the oligomer, wherein the wt % of the hydrophilic polymer and oligomer are based on the film composition exclusive of the active agent; and

an effective amount of an active agent,

wherein the blend and the rapidly dissolving material are effective to facilitate dissolution of the film within 10 minutes following application of the film to a moist body surface.

56. The film of claim 55, wherein the hydrophilic polymer is selected from poly(N-vinyl lactams), poly(N-vinyl amides), poly(N-alkylacrylamides), and copolymers and blends thereof.

57. The film of claim 55, wherein the hydrophilic polymer is a poly(N-vinyl lactam).

58. The film of claim 57, wherein the poly(N-vinyl lactam) is polyvinyl pyrrolidone.

59. The film of claim 58, wherein the hydrophilic polymer has a number average molecular weight in the range of approximately 100,000 to 2,000,000.

60. The film of claim 55, wherein the rapidly dissolving polymeric material is selected from oligosaccharides, polysaccharides, crosslinked polyvinylpyrrolidone, alginic acid, agar, and bentonite.

61. The film of claim 55, wherein the active agent is for treatment of a condition involving teeth or surrounding tissue.