Sublingual and buccal film compositions

• US 10,821,074 B2
• Filed: 07/28/2018
• Issued: 11/03/2020
• Est. Priority Date: 08/07/2009
• Status: Active Grant

• Current Assignee: Aquestive Therapeutics, Inc.
• Original Assignee: Aquestive Therapeutics, Inc.
• Inventors: Myers, Garry L., Hilbert, Samuel D., Boone, Bill J., Bogue, B. Arlie, Sanghvi, Pradeep, Hariharan, Madhusudan
• Primary Examiner(s): Epps-Smith, Janet L
• Application Number:
  US16/048,243
• Publication Number:
  US 20190070100A1
• Time in Patent Office: 829 Days
• Field of Search: 514289, 514321, 514404, 514415, 424422, 424434, 424435, 424484
• 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 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 25/04 Centrally acting analgesics, e.g. opioids

Abstract

The present invention relates to products and methods for treatment of various symptoms in a patient, including treatment of pain suffered by a patient. The invention more particularly relates to self-supporting dosage forms which provide an active agent while providing sufficient buccal adhesion of the dosage form. Further, the present invention provides a dosage form which is useful in reducing the likelihood of diversion abuse of the active agent.

Claims

1. A self-supporting film dosage composition comprising:

a. a polymeric carrier matrix;

b. a therapeutically effective amount of apomorphine or a pharmaceutically acceptable salt thereof as an agonist; and

c. a buffer, wherein the ratio of said buffer to apomorphine or a pharmaceutically acceptable salt thereof is from about 2;

1 to about 1;

5, the self-supporting film dosage composition comprising at least a first region and at least a second region, wherein the at least first region and the at least second region are arranged in a film dosage, the agonist is contained in at least the first region and the buffer is contained in at least the second region; and

said film dosage provides a local pH of between about 5 to about 9; and

wherein said self-supporting film dosage composition disperses in an oral cavity in about 30 minutes or less.

2. The self-supporting film dosage composition of claim 1, wherein said composition contains from about 2 to about 16 mg of apomorphine or a pharmaceutically acceptable salt thereof.

3. The self-supporting film dosage composition of claim 1, wherein said composition disperses and dissolves in the oral cavity between about 1 minute and about 3 minutes.

4. The self-supporting film dosage composition of claim 1, wherein said polymeric carrier matrix comprises polyethylene oxide, pullulan, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polysaccharide, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, or a combination thereof.

5. The self-supporting film dosage composition of claim 1, wherein said composition further comprises an FD&

C coloring agent, coloring agent, oxide of titanium, sucralose, and glycerol, glycerol monoacetate, diacetate or triacetate, a mono-glyceride with a C₁₈-fatty acid, triacetin, polysorbate, cetyl alcohol, propylene glycol, sorbitol, sodium diethylsulfosuccinate, triethyl citrate, or tributyl citrate.

6. The self-supporting film dosage composition of claim 1, wherein said composition further comprises glycerol.

7. The self-supporting film dosage composition of claim 1, wherein said self-supporting film dosage composition has a thickness of from 0.1 to 10 mils.

8. The self-supporting film dosage composition of claim 1, wherein the dosage contains regions of differing dissolution rates and the composition is a dual region product.

9. The self-supporting film dosage composition of claim 1, wherein the buffer includes a first buffering system.

10. The self-supporting film dosage composition of claim 9, wherein the self-supporting film dosage composition further includes a second buffering system.

11. A self-supporting film dosage composition comprising:

a polymeric carrier matrix comprising polyethylene oxide, pullulan, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polysaccharide, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, or a combination thereof;

a therapeutically effective amount of apomorphine or a pharmaceutically acceptable salt thereof as an agonist, and a buffer, wherein the ratio of said buffer to apomorphine or a pharmaceutically acceptable salt thereof is from about 2;

1 to about 1;

5, the self-supporting film dosage composition comprising at least a first region and at least a second region, wherein the at least first region and the at least second region are arranged in a film dosage, the agonist is contained in at least the first region and the buffer is contained in at least the second region; and

said film dosage provides a local pH of between about 5 to about 9; and

wherein said self-supporting film dosage composition disperses in an oral cavity in about 30 minutes or less.

12. The self-supporting film dosage composition of claim 11, wherein said composition further comprises glycerol, glycerol monoacetate, diacetate or triacetate, a mono-glyceride with a C₁₈-fatty acid, triacetin, polysorbate, cetyl alcohol, propylene glycol, sorbitol, sodium diethylsulfosuccinate, triethyl citrate, or tributyl citrate and wherein said composition further comprises a sweetener.

13. The self-supporting film dosage composition of claim 12, wherein said composition further comprises an FD&

C coloring agent, coloring agent, oxide of titanium, glycerol and sucralose.

14. The self-supporting film dosage composition of claim 11, wherein the composition comprises about 2 to about 16 mg of apomorphine or a pharmaceutically acceptable salt thereof.

15. The self-supporting film dosage composition of claim 11, wherein said composition disperses and dissolves in the oral cavity between about 1 minute and about 3 minutes.

16. The self-supporting film dosage composition of claim 11, wherein said self-supporting film dosage composition has a thickness of from 0.1 to 10 mils.

17. The self-supporting film dosage composition of claim 11, wherein the dosage contains regions of differing dissolution rates.

18. The self-supporting film dosage composition of claim 11, wherein the composition is a dual region product.

19. The self-supporting film dosage composition of claim 11, wherein the buffer includes a first buffering system and the self-supporting film dosage composition further includes a second buffering system.

20. A self-supporting film dosage composition comprising:

a polymeric carrier matrix comprising polyethylene oxide, pullulan, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polysaccharide, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, or a combination thereof; and

a therapeutically effective amount of apomorphine or a pharmaceutically acceptable salt thereof as an agonist and a buffer, wherein the ratio of said buffer to apomorphine or a pharmaceutically acceptable salt thereof is from about 2;

1 to about 1;

5, the self-supporting film dosage composition comprising at least a first region and at least a second region, wherein the at least first region and the at least second region are arranged in a film dosage, the agonist is contained in at least the first region and the buffer is contained in at least the second region; and

said film dosage provides a local pH of between about 5 to about 9; and

wherein the film is mucoadhesive to the sublingual mucosa or the buccal mucosa;

wherein said composition further comprises glycerol and sucralose and wherein said self-supporting film dosage composition disperses in an oral cavity in about 30 minutes or less.

21. A self-supporting film dosage composition comprising:

a polymeric carrier matrix comprising hydroxypropylmethyl cellulose, hydroxyethyl cellulose, polysaccharide, a coloring agent, glycerol, sucralose, a mono-glyceride with a C₁₈-fatty acid, and a flavoring agent;

a therapeutically effective amount of apomorphine or a pharmaceutically acceptable salt thereof as an agonist; and

a buffer, wherein the ratio of said buffer to apomorphine or a pharmaceutically acceptable salt thereof is from about 2;

1 to about 1;

5, the self-supporting film dosage composition comprising at least a first region and at least a second region, wherein the at least first region and the at least second region are arranged in a film dosage, the agonist is contained in at least the first region and the buffer is contained in at least the second region; and

said film dosage provides a local pH of between about 5 to about 9;

the film is mucoadhesive to the sublingual mucosa or the buccal mucosa;

said self-supporting film dosage composition disperses in an oral cavity in about 30 minutes or less, wherein the dosage contains regions of differing dissolution rates and the composition is a dual region product.