Polyethylene oxide-based films and drug delivery systems made therefrom

• US 7,666,337 B2
• Filed: 05/28/2004
• Issued: 02/23/2010
• 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.
• Primary Examiner(s): Lee; Edmund H.
• Application Number:
  US10/856,176
• Publication Number:
  US 20050037055A1
• Time in Patent Office: 2,097 Days
• Field of Search: None
• US Class Current: 264/172.19
• 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 process for making a film having a substantially uniform distribution of components, comprising the steps of:

(a) forming a flowable polymer matrix comprising a water-soluble polymer composition comprising polyethylene oxide, at least 30% solvent and an active component, said matrix having a uniform distribution of said active component;

(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 uniform distribution of said active component by locking-in or substantially preventing migration of said active component 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 uniform distribution of active by said locking-in or substantially preventing migration of said active component is maintained.

2. The process according to claim 1, wherein the step of casting said matrix comprises casting onto a surface having top and bottom sides.

3. The process according to claim 2, wherein the step of evaporating further comprises applying heat to said bottom side of said surface.

4. The process according to claim 1, wherein said water-soluble polymer comprises at least about 20% by weight polyethylene oxide.

5. The process according to claim 1, wherein said water-soluble polymer comprises about 20% to about 100% by weight polyethylene oxide.

6. The process according to claim 1, further comprising a hydrophilic cellulosic polymer present in the amount of about 0% to about 80% by weight of said water-soluble polymer composition, wherein said hydrophilic cellulosic polymer is selected from the group consisting of hydroxypropylmethyl cellulose, hydroxypropyl cellulose and combinations thereof.

7. The process according to claim 6, wherein said water-soluble polymer composition comprises said hydrophilic cellulosic polymer in a ratio of up to about 4:

1 with polyethylene oxide.

8. The process according to claim 1, wherein said water-soluble polymer composition comprises polyethylene oxide having a molecular weight of about 100,000 to about 900,000.

9. The process according to claim 1, wherein said water-soluble polymer composition comprises polyethylene oxide having a molecular weight of about 100,000 to about 4 million.

10. The process according to claim 1, wherein said water-soluble polymer composition 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.

11. The process according to claim 1, wherein said water-soluble polymer composition comprises at least 1 mg polyethylene oxide.

12. The process according to claim 1, wherein said water-soluble polymer composition comprises no greater than about 200 mg polyethylene oxide.

13. The process according to claim 1, wherein said active component is selected from the group consisting of cosmetic agents, pharmaceutical agents, bioactive agents, and combinations thereof.

14. The process according to claim 1, wherein said matrix of step (a) further comprises a densifying agent.

15. The process according to claim 14, wherein said densifying agent is simethicone.

16. The process according to claim 1, wherein said matrix of step (a) further comprises a solubility enhancing agent.

17. The process according to claim 1, wherein said water-soluble polymer composition consists essentially of polyethylene oxide in the amount of about 20% to about 100% by weight of the polymer composition and a hydrophilic cellulosic polymer selected from the group consisting of hydroxypropylmethyl cellulose, hydroxypropyl cellulose and combinations thereof in the amount of about 0% to about 80% by weight of the polymer composition.

18. The process according to claim 1, wherein said matrix of step (a) further comprises an anti-foaming or surface-tension reducing agent and is free of bubbles.

19. The process according to claim 1, wherein the temperature of said matrix is 100°

C. or less.

20. The process according to claim 1, wherein said resulting film has a thickness of about 2 mils to about 10 mils.

21. The process of claim 1, wherein said evaporating is conducted by applying radiant energy selected from the group consisting of air currents, heat, infrared radiation, radio frequency radiation and combinations thereof.

22. The process of claim 1, wherein said visco-elastic film is further dried.

23. The process of claim 1, wherein said visco-elastic film is a solid.

24. The process of claim 1, wherein said visco-elastic film is formed within about 4 minutes.

25. 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 water-soluble polymer, a solvent and an active, said matrix having a 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 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 uniform distribution of active by said locking-in or substantially preventing migration of said active is maintained.

26. The process according to claim 25, wherein said resulting film has a thickness of about 2 mils to about 10 mils.

27. The process of claim 25, wherein said evaporating is conducted by applying radiant energy selected from the group consisting of air currents, heat, infrared radiation, radio frequency radiation and combinations thereof.

28. The process of claim 25, wherein the visco-elastic film is formed within about 4 minutes.

29. The process of claim 25, wherein the visco-elastic film is further dried.

30. The process of claim 25, wherein the visco-elastic film is a solid.