Methods for modulating dissolution, bioavailability, bioequivalence and drug delivery profile of thin film drug delivery systems, controlled-release thin film dosage formats, and methods for their manufacture and use

• US 8,999,372 B2
• Filed: 03/07/2006
• Issued: 04/07/2015
• Est. Priority Date: 11/14/2002
• Status: Active Grant

• Current Assignee: CURE Pharmaceutical Incorporated
• Original Assignee: Cura Pharmaceutical Company Incorporated
• Inventors: Davidson, Robert S., Kehoe, Gary
• Primary Examiner(s): Fubara, Blessing M
• Application Number:
  US11/371,167
• Publication Number:
  US 20060210610A1
• Time in Patent Office: 3,318 Days
• Field of Search: 424/439
• US Class Current: 424/439
• CPC Class Codes: A61K 31/451 having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
• 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 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• 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 47/36 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 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 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence

Abstract

Methods for modulating dissolution, bioavailability, bioequivalence and drug delivery profile of thin film drug delivery systems, controlled-release thin film dosage formats, and methods for their manufacture and use are disclosed.

Claims

1. A composition for the oral administration of an active ingredient wherein the composition comprises an edible thin film, the film comprising a natural or synthetic water-soluble polymer, the film having a thickness of 0.01 mm -3.00 mm and exhibiting a rapid dissolution rate in the oral cavity and an active ingredient provided in controlled release formulation as a coating on said thin film, wherein the coating comprises a powder matrix comprising the active ingredient in a microencapsulated form.

2. The composition of claim 1, wherein the active ingredient is provided in a controlled-release formulation selected from the group consisting of slow-, medium-, fast- and delayed release, and a combination thereof.

3. The composition of claim 1, wherein the active ingredient is microencapsulated by a process selected from the group consisting of simple or complex coacervation, interracial cross-linking, interracial polymerization, polymer dispersion, matrix encapsulation, solvent evaporation, solvent extraction, spray drying, hot melt microencapsulation and supercritical fluid.

4. A dosage format for the oral administration of an active ingredient, the dosage format comprising:

a) an edible thin film, the film comprising a natural or synthetic water-soluble polymer; and

b) a multiplicity of individual microencapsulated controlled-release units each comprising the active ingredient and contained within the thin film;

wherein the thin film is formulated and formed such that the thin film disintegrates in the oral cavity within about 15 seconds and wherein the multiplicity of individual active ingredient controlled-release units contained in the thin film are released upon said oral disintegration of the thin film, so that the active ingredient is released at a time other than immediately following oral administration.

5. The dosage format of claim 4, wherein the microencapsulated controlled-release units are encapsulated with ethyl cellulose, cellulose acetate phthalate, cellulose acetate butyrate, hydroxypropyl methyl cellulose phthalate, carboxymethyl ethyl cellulose, or carrageenan, or a mixture thereof.

6. The dosage format of claim 5, wherein the microencapsulated controlled-release units are encapsulated with ethyl cellulose, or carrageenan, or a mixture thereof.

7. The dosage format of claim 5, wherein the micro-encapsulated controlled-release units are encapsulated by a coacervation process.

8. The dosage format of claim 7, wherein a second polymeric material is used in the coacervation process, the second polymer comprising polyethylene, polyisobutylene, ethylenevinyl acetate, or a mixture thereof.

9. The dosage format of claim 5, wherein the micro-encapsulated controlled-release units are encapsulated by a solvent evaporation and solvent extraction process.

10. The dosage format of claim 5, wherein the micro-encapsulated controlled-release units are encapsulated by a hot melt microencapsulation process.

11. The dosage format of claim 5, wherein the micro-encapsulated controlled-release units have particle sizes in the range of 40 μ

m to 250 μ

m.

12. The dosage format of claim 4, further comprising a permeation enhancer.

13. The dosage format of claim 12, wherein the permeation enhancer is a bile salt, an alkylsulfate surfactant, or dimethyl sulfoxide, or any combination thereof.

14. The dosage format of claim 13, wherein the bile salt is sodium cholate, sodium glycocholate, sodium glyodeoxycholate, tautodeoxycholate, sodium deoxycholate, sodium thocholate chenocholate, hyodeoxycholate, dehydrocholate, glycochenocholate, taurochenocholate, or taurochenodexoxycholate, or any combination thereof.

15. The dosage format of claim 13, wherein the alkylsulfate surfactant is sodium dodecyl sulfate or sodium lauryl sulfate.

16. The dosage format of claim 4, further comprising an agent for adjusting pH conditions to modulate the rate of mucosal absorption of active ingredient.

17. The dosage format of claim 16, wherein the agent for adjusting pH conditions is a buffering agent.

18. The dosage format of claim 16, wherein the agent for adjusting pH conditions is contained in the film layer, in the controlled release units, or both.

19. The dosage format of claim 4, further comprising an immediate release form of the active agent, of a second active agent, or both.

20. The dosage format of claim 4, wherein the active ingredient in the controlled-release units is made available in the gastrointestinal tract.