Polyethylene oxide-based films and drug delivery systems made therefrom

• US 20050037055A1
• Filed: 05/28/2004
• Published: 02/17/2005
• Est. Priority Date: 04/11/2002
• Status: Active Grant

• Current Assignee: Aquestive Therapeutics, Inc.
• Original Assignee: Monosol Rx LLC (Kuraray Company Limited)
• Inventors: Yang, Robert K., Fuisz, Joseph M., Fuisz, Richard C., Myers, Gary L.
• Granted Patent: US 7,666,337 B2
• Time in Patent Office: Days
• US Class Current: 424/443
• CPC Class Codes: A61K 2800/92 Oral administration
• CPC Class Codes: A61K 8/0216 Solid or semisolid forms
• CPC Class Codes: A61K 8/731 Cellulose; Quaternized cellulose derivatives
• CPC Class Codes: A61K 8/86 Polyethers
• 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
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: A61Q 11/00 : Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
• CPC Class Codes: C08J 2371/02 : Polyalkylene oxides
• CPC Class Codes: C08J 5/18 : Manufacture of films or sheets
• CPC Class Codes: F26B 13/104 : supported by fluid jets only; Fluid blowing arrangements for flotation dryers, e.g. coanda nozzles

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.

Claims

1. A rapid-dissolve film product comprising:

at least one water-soluble polymer comprising polyethylene oxide alone or in combination with a hydrophilic cellulosic polymer,

wherein said film product is free of added plasticizers.

2. The film product according to claim 1, wherein said film product is free of added surfactants and polyalcohols.

3. The film product according to claim 1, wherein said at least one water-soluble polymer comprises at least about 20% by weight polyethylene oxide.

4. The film product according to claim 1, wherein said at least one water-soluble polymer comprises up to about 100% by weight polyethylene oxide.

5. The film product according to claim 1, wherein said at least one water-soluble polymer comprises up to about 80% by weight polyethylene oxide.

6. The film product according to claim 1, wherein said hydrophilic cellulosic polymer comprises about 0% to about 80% hydroxypropylmethyl cellulose.

7. The film product according to claim 1, wherein said hydrophilic cellulosic polymer comprises about 0% to about 80% hydroxypropyl cellulose.

8. The film product according to claim 1, wherein said water-soluble polymer comprises said hydrophilic cellulosic polymer in a ratio of up to about 4:

1 with polyethylene oxide.

9. The film product according to claim 1, wherein said at least one water-soluble polymer comprises polyethylene oxide having a molecular weight of about 100,000 to about 900,000.

10. The film product according to claim 1, wherein said at least one water-soluble polymer comprises polyethylene oxide having a molecular weight of about 100,000 to about 4 million.

11. The film product according to claim 1, wherein said at least one water-soluble polymer comprises polyethylene oxide having a molecular weight of about 100,000 to about 300,000 in combination with polyethylene oxide having a molecular weight of about 600,000 to about 900,000.

12. The film product according to claim 1, wherein said at least one water-soluble polymer comprises at least 1 mg polyethylene oxide.

13. The film product according to claim 1, wherein said at least one water-soluble polymer comprises no greater than about 200 mg polyethylene oxide.

14. The film product according to claim 1, further comprising an active component selected from the group consisting of cosmetic agents, pharmaceutical agents, bioactive agents, and combinations thereof.

15. The film product according to claim 14, wherein said active component is loratadine.

16. The film product according to claim 14, wherein said bioactive agents are selected from the group consisting of enzymes, antigens, and allergens.

17. The film product according to claim 1, further comprising a densifying agent.

18. The film product according to claim 17, wherein said densifying agent is simethicone.

19. The film product according to claim 1, further comprising a solubility enhancing agent.

20. The film product according to claim 1, wherein said film is resistant to tearing when dried.

21. The film product according to claim 1, wherein said film is flexible when dried.

22. The film product according to claim 1, wherein said at least one water-soluble polymer comprises polyethylene oxide and hydroxypropyl cellulose in amounts sufficient to prevent adhesion to mucosal tissue.

23. The film product according to claim 1, wherein said at least one water-soluble polymer comprises polyethylene oxide in amounts sufficient to promote adhesion to mucosal tissue.

24. A rapid-dissolve film product comprising:

at least one water-soluble polymer comprising PEO alone or in combination with a second polymer component,

wherein said film is free of added plasticizers.

25. A rapid-dissolve film product comprising:

at least one water-soluble polymer comprising about 20% to 100% by weight polyethylene oxide, about 0% to 80% by weight hydroxypropylmethyl cellulose, and about 0% to 80% by weight hydroxypropyl cellulose;

an active component;

sucralose;

precipitated calcium carbonate;

at least one flavoring;

simethicone;

water; and

at least one colorant,

wherein said film product is free of added plasticizers, surfactants, and polyalcohols.

26. An edible water-soluble delivery system in the form of a film composition, comprising:

at least one water-soluble polymer comprising polyethylene oxide alone or in combination with a polymer selected from the group consisting of hydroxypropylmethyl cellulose and hydroxypropyl cellulose,

wherein said edible water-soluble delivery system is essentially free of organic solvents, plasticizers, surfactants, and polyalcohols.

27. The edible water-soluble delivery system according to claim 26, further comprising an active component selected from the group consisting of cosmetic agents, pharmaceutical agents, bioactive agents, and combinations thereof.

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

(a) combining at least one water-soluble polymer comprising polyethylene oxide alone or in combination with a hydrophilic cellulosic polymer, a solvent, and an active component to form a matrix with a uniform distribution of said components;

(b) forming a film from said matrix; and

(c) drying said film,

wherein said film is free of added plasticizers.

29. The process according to claim 28, wherein the step of forming a film from said matrix further comprises casting said matrix onto a surface having top and bottom sides.

30. The process according to claim 28, wherein the step of drying said film further comprises applying heat to said bottom side of said surface.

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

(a) combining at least one water-soluble polymer comprising polyethylene oxide alone or in combination with a hydrophilic cellulosic polymer, and an active component to form a matrix with a uniform distribution of said components; and

(b) extruding said matrix to form a film,

wherein said film is free of added plasticizers.

32. The process according to claim 31, further comprising the step of cooling said extruded film.

33. A rapid-dissolve, flexible film product being formed by the steps of:

(a) combining at least one water-soluble polymer comprising polyethylene oxide alone or in combination with a hydrophilic cellulosic polymer, a solvent, and an active component to form a matrix with a uniform distribution of said components;

(b) forming a film from said matrix; and

(c) drying said film,

wherein said film is free of added plasticizers.

34. A premixture of a hydrophilic cellulosic polymer in a ratio of up to about 4:

1 with polyethylene oxide, which when deposited as a film and dried forms a rapid-dissolve delivery system for active components.

35. A final film product comprising at least one water-soluble polymer comprising polyethylene oxide alone or in combination with a hydrophilic cellulosic polymer, which can be randomly divided and wherein no divided-out portion varies more than about 10% in composition of components.

36. A final film product comprising at least one water-soluble polymer comprising polyethylene oxide alone or in combination with a hydrophilic cellulosic polymer, which can be randomly divided and wherein no divided-out portion varies more than about 10% in active components.