SUBLINGUAL AND BUCCAL FILM COMPOSITIONS

• US 20160113885A1
• Filed: 01/06/2016
• Published: 04/28/2016
• Est. Priority Date: 08/07/2009
• Status: Active Grant

• Current Assignee: Indivior UK Limited (Indivior Plc)
• Original Assignee: Indivior UK Limited (Indivior Plc)
• Inventors: Myers, Garry L., Hilbert, Samuel D., Boone, Bill J., Bogue, Beuford Arlie, Hariharan, Madhusudan, Sanghvi, Pradeep
• Granted Patent: US 9,687,454 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4355 the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• 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 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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 9/006 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: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/36 Opioid-abuse

Abstract

The present invention relates to products and methods for treatment of narcotic dependence in a user. The invention more particularly relates to self-supporting dosage forms which provide an active agent for treating narcotic dependence while providing sufficient buccal adhesion of the dosage form.

Claims

1. A method for treating an opioid narcotic dependence in a patient in need thereof comprising sublingually or buccally administering a mucoadhesive film to a sublingual or buccal mucosal tissue of the patient to treat the opioid narcotic dependence;

wherein the film comprises a polymeric matrix, about 2 mg to about 16 mg buprenorphine or a pharmaceutically acceptable salt thereof, naloxone or a pharmaceutically acceptable salt thereof, and a buffer;

wherein absorption of the buprenorphine through the sublingual or buccal mucosal tissue is maximized to produce a Cmax from about 0.624 ng/ml and about 5.638 ng/ml and an AUC from about 5.431 hr*ng/ml to about 56.238 hr*ng/ml in the patient; and

wherein absorption of the naloxone or the pharmaceutically acceptable salt thereof through the sublingual or buccal mucosal tissue is minimized or inhibited.

2. The method of claim 1, wherein the ratio of buprenorphine to naloxone is about 6:

1 to 2;

1.

3. The method of claim 1, wherein the polymeric matrix comprises a water-soluble polymer.

4. The method of claim 1, wherein the mucoadhesive film comprises at least 25 wt % of a polymeric matrix, and wherein the polymeric matrix comprises a water-soluble polymer.

5. The method of claim 1, wherein the film comprises about 0.5 mg to about 4 mg of the naloxone or the pharmaceutically acceptable salt thereof.

6. The method of claim 1, wherein the buffer comprises sodium citrate, citric acid, or a combination thereof.

7. The method of claim 1, wherein the buffer comprises acetic acid, sodium acetate, or a combination thereof.

8. The method of claim 1, wherein the polymeric matrix comprises a water-soluble polymer selected from the group consisting of polyethylene oxide, pullulan, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragancanth guam, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, or combinations thereof.

9. The method of claim 3, wherein the water-soluble polymer is polyethylene oxide having a molecular weight from about 100,000 to about 900,000.

10. A method for treating an opioid narcotic dependence in a patient in need thereof comprising sublingually or buccally administering a mucoadhesive film to a sublingual or buccal mucosal tissue of the patient to treat the opioid narcotic dependence;

wherein the film comprises at least 25 wt % of a water-soluble polymer, about 2 mg to about 16 mg buprenorphine or a pharmaceutically acceptable salt thereof, about 0.5 mg to about 4 mg naloxone or a pharmaceutically acceptable salt thereof, and a buffer;

wherein the water-soluble polymer is polyethylene oxide, pullulan, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragancanth guam, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, or combinations thereof;

wherein absorption of the buprenorphine through the sublingual or buccal mucosal tissue is maximized to produce a Cmax from about 0.624 ng/ml and about 5.638 ng/ml and an AUC from about 5.431 hr*ng/ml to about 56.238 hr*ng/ml in the patient; and

wherein absorption of the naloxone or the pharmaceutically acceptable salt thereof through the sublingual or buccal mucosal tissue is minimized or inhibited.