Film compositions for delivery of actives

• US 8,663,687 B2
• Filed: 05/13/2010
• Issued: 03/04/2014
• Est. Priority Date: 10/12/2001
• Status: Expired due to Term

• Current Assignee: Aquestive Therapeutics, Inc.
• Original Assignee: Monosol Rx LLC (Kuraray Company Limited)
• Inventors: Myers, Garry L., Fuisz, Richard C.
• Primary Examiner(s): FISHER, ABIGAIL L
• Application Number:
  US12/779,316
• Publication Number:
  US 20100221309A1
• Time in Patent Office: 1,391 Days
• Field of Search: 424/484, 424/486, 424/487, 424/434, 424/400
• US Class Current: 424/484
• CPC Class Codes: A61K 2800/413 Nanosized, i.e. having sizes below 100 nm
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• 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 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 8/0204 Specific forms not provided for by any of groups A61K8/0208 - A61K8/14
• CPC Class Codes: A61K 8/0208 Tissues; Wipes; Patches
• CPC Class Codes: A61K 8/0216 Solid or semisolid forms
• CPC Class Codes: A61K 8/0291 Micelles
• CPC Class Codes: A61K 8/0295 Liquid crystals
• CPC Class Codes: A61K 8/355 Quinones
• CPC Class Codes: A61K 8/731 Cellulose; Quaternized cellulose derivatives
• CPC Class Codes: A61K 8/86 Polyethers
• 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: A61Q 15/00 Anti-perspirants or body deodorants deodorisation of air A61L9/00
• CPC Class Codes: A61Q 17/005 Antimicrobial preparations
• CPC Class Codes: A61Q 17/02 containing insect repellants
• CPC Class Codes: A61Q 17/04 Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: A61Q 19/10 Washing or bathing preparations
• CPC Class Codes: A61Q 5/02 Preparations for cleaning the hair
• CPC Class Codes: A61Q 5/06 : Preparations for styling the hair, e.g. by temporary shaping or colouring
• CPC Class Codes: A61Q 5/12 : Preparations containing hair conditioners
• CPC Class Codes: A61Q 9/02 : Shaving preparations
• CPC Class Codes: B29C 41/28 : by depositing flowable material on an endless belt
• CPC Class Codes: B29K 2001/00 : Use of cellulose, modified cellulose or cellulose derivatives, e.g. viscose, as moulding material
• CPC Class Codes: B29K 2001/12 : Cellulose acetate
• CPC Class Codes: B29K 2003/00 : Use of starch or derivatives as moulding material
• CPC Class Codes: B29K 2005/00 : Use of polysaccharides or derivatives as moulding material
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

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. Desirably, the films contain at least one active agent, which may be administered to a user topically, transmucosally, vaginally, ocularly, aurally, nasally, transdermally or orally.

Claims

1. A self-supporting film composition comprising:

(i) a water soluble polymer composition comprising polyethylene oxide and a saccharide-based polymer; and

(ii) a topical agent;

wherein said topical agent is in the form of a small-scale particle selected from the group consisting of at least one type of nanoparticle, at least one type of micelle, at least one type of microdroplet, at least one type of microparticle, at least one type of liquid crystal, and combinations thereof, and

wherein said small-scale particle of at least one agent is uniformly distributed in the film composition and uniformity is measured by equally sized individual unit doses which do not vary by more than 10% by weight of said small-scale particle of at least one agent from a desired dose.

2. The composition of claim 1, wherein said topical agent is in the form of at least one type of liquid crystal.

3. The composition of claim 1, wherein said topical agent is in the form of at least one type of micelle.

4. The composition of claim 1, wherein said topical agent is bound to at least one ligand.

5. A dosage composition comprising:

a. A self-supporting film comprising;

i. At least one polymer; and

ii. At least one agent;

wherein said at least one agent is in the form of a small-scale particle selected from the group consisting of at least one type of nanoparticle, at least one type of micelle, at least one type of microdroplet, at least one type of microparticle, at least one type of liquid crystal, and combinations thereof, and

wherein said small-scale particle of at least one agent is uniformly distributed in the dosage composition and uniformity is measured by equally sized individual unit doses which do not vary by more than 10% by weight of said small-scale particle of at least one agent from a desired dose.

6. The composition of claim 5, wherein said agent is in the form of at least one type of liquid crystal.

7. The composition of claim 5, wherein said agent is in the form of at least one type of micelle.

8. The composition of claim 5, wherein said agent is bound to at least one ligand.

9. A method of forming a self-supporting film dosage composition, comprising the steps of:

a. Providing a polymeric matrix;

b. Forming a small-scale form of at least one agent;

c. Dispersing said small-scale form of at least one agent throughout said polymeric matrix;

d. Drying said polymeric matrix so as to form a self-supporting film dosage composition comprising said small-scale form of at least one agent;

wherein said small-scale form of at least one agent is selected from the group consisting of at least one type of nanoparticle, at least one type of microparticle, at least one type of microdroplet, at least one type of micelle, at least one type of liquid crystal, and combinations thereof, and

wherein said small-scale form of at least one agent is uniformly distributed in the film dosage composition and uniformity subsequent to dispersing and drying is measured by equally sized individual unit doses which do not vary by more than 10% by weight of said small-scale form of at least one agent from a desired dose.

10. The method of claim 9, wherein said agent is in the form of at least one type of microdroplet.

11. The method of claim 9, wherein said agent is in the form of at least one type of micelle.

12. The method of claim 9, wherein said small-scale form of at least one agent is formed through emulsion processing.

13. The method of claim 9, wherein said small-scale form of at least one agent is formed through milling.

14. The method of claim 9, wherein said small-scale form of at least one agent is formed through processing via a microfluidics pumping apparatus.

15. The method of claim 9, wherein said small-scale form of at least one agent is bound to at least one ligand.

16. The method of claim 9, wherein said step of drying said polymeric matrix comprises heating said polymeric matrix so as to rapidly form a visco-elastic mass to maintain a uniform distribution of said agent by locking-in or preventing migration of said agent within said visco-elastic mass within the first 10 minutes or less to maintain a uniform distribution of said agent by locking-in or preventing migration of said agent within said visco-elastic mass.

17. The method of claim 16, wherein said polymeric matrix containing said agent varies no more than 10% by weight of said agent throughout said polymeric matrix.

18. The method of claim 16, wherein said step of drying said polymeric matrix further comprises further drying said visco-elastic mass so as to provide a self-supporting film dosage composition having a solvent content of 10% or less.

19. The method of claim 16, wherein said step of forming a visco-elastic mass occurs within the first 0.5 to about 10 minutes of heating to maintain a uniform distribution of said agent by locking-in or preventing migration of said agent within said visco-elastic mass.

20. The method of claim 19, wherein said polymeric matrix containing said agent varies no more than 10% by weight of said agent throughout said polymeric matrix.

21. The method of claim 19, wherein said step of drying said polymeric matrix further comprises further drying said visco-elastic mass so as to provide a self-supporting film dosage composition having a solvent content of 10% or less.

22. The method of claim 9, wherein said small-scale form of at least one agent is formed through processing via a high shear apparatus.

23. The method of claim 9, wherein said small-scale form of said agent is in the form of at least one liquid crystal.

24. A method of forming a self-supporting film dosage composition, comprising the steps of:

a. Providing a polymeric matrix;

b. Forming a small-scale form of at least one agent;

c. Applying said small-scale form of at least one agent to said polymeric matrix via deposition; and

d. Drying said polymeric matrix so as to form a self-supporting film dosage composition comprising said small-scale form of at least one agent,

wherein said small-scale form of at least one agent is selected from the group consisting of at least one type of nanoparticle, at least one type of micelle, at least one type of microdroplet, at least one type of microparticle, at least one type of liquid crystal, and combinations thereof, and

wherein said small-scale form of at least one agent is uniformly distributed on the film dosage composition and uniformity subsequent to applying and drying is measured by equally sized individual unit doses which do not vary by more than 10% by weight of said small-scale form of at least one agent from a desired dose.

25. The method of claim 24, wherein said agent is in the form of at least one type of microdroplet.

26. The method of claim 24, wherein said agent is in the form of at least one type of micelle.

27. The method of claim 24, wherein said small-scale form of at least one agent is formed through emulsion processing.

28. The method of claim 24, wherein said small-scale form of at least one agent is formed through milling.

29. The method of claim 24, wherein said small-scale form of at least one agent is formed through processing via a microfluidics pumping apparatus.

30. The method of claim 24, wherein said small-scale form of at least one agent is bound to at least one ligand.

31. The method of claim 24, wherein said small-scale form of at least one agent is formed through processing via a high shear apparatus.

32. The method of claim 24, wherein said small-scale form of said agent is in the form of at least one liquid crystal.