Sublingual and buccal film compositions

• US 10,285,910 B2
• Filed: 10/17/2018
• Issued: 05/14/2019
• Est. Priority Date: 10/12/2001
• Status: Expired due to Fees

• Current Assignee: Aquestive Therapeutics, Inc.
• Original Assignee: Aquestive Therapeutics, Inc.
• Inventors: Yang, Robert K., Fuisz, Richard C., Myers, Garry L., Fuisz, Joseph M.
• Primary Examiner(s): Packard, Benjamin J
• Application Number:
  US16/163,029
• Publication Number:
  US 20190046411A1
• Time in Patent Office: 209 Days
• CPC Class Codes: A61J 3/00 Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
• 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: B29C 48/08 flexible, e.g. films
• CPC Class Codes: B29C 48/91 Heating, e.g. for cross linking
• CPC Class Codes: B29C 48/919 using a bath, e.g. extruding into an open bath to coagulate or cool the material
• CPC Class Codes: F26B 13/10 Arrangements for feeding, heating or supporting materials; Controlling movement, tension or position of materials heating processes F26B3/00
• CPC Class Codes: F26B 13/104 supported by fluid jets only; Fluid blowing arrangements for flotation dryers, e.g. coanda nozzles

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 drug delivery composition for making a plurality of individual unit doses in a self-supporting film dosage form, which plurality of individual unit doses being cut from a self-supporting film not made in a mold or well having at least one particulate active substantially uniformly stationed in said film, each of said individual unit doses containing a desired amount of said at least one particulate active, said composition comprising:

a. a polymeric carrier matrix comprising polyethylene oxide and polyvinylpyrrolidone;

b. naloxone or a pharmaceutical salt thereof;

c. the at least one particulate active selected from the group consisting of analgesics, narcotics, opiates, and opiate derivatives;

d. citric acid;

e. an antioxidant;

f. a sweetener selected from the group consisting of acesulfame potassium salt, sodium saccharin, sucralose, aspartame and combinations thereof;

g. at least one coloring agent selected from the group consisting of FD&

C colors, D&

C colors, and combinations thereof;

h. at least one flavor;

i. a hydrogenated starch hydrolysate; and

j. disodium phosphate,

wherein said uniformity of the film from which the plurality of individual unit doses is cut is measured by substantially equally sized individual unit doses cut from the film which do not vary by more than 10% of a desired amount of said at least one particulate active.

2. The composition of claim 1, further comprising propylene glycol, shellac, or a combination thereof.

3. The composition of claim 1, wherein the antioxidant is selected from the group consisting of BHT, BHA, citric acid, propyl gallate, sodium sulfate, sodium metabisulfite, ascorbic acid, tocopherol, tocopherol ester derivatives, 2-mercaptobenzimidazole, and combinations thereof.

4. The composition of claim 1, wherein the at least one flavor comprises a lemon-lime flavor.

5. The composition of claim 1, wherein the at least one flavor comprises a component selected from the group consisting of alpha-citral, beta-citral, decanal, aldehyde C-8, aldehyde C-9, aldehyde C-12, and combinations thereof.

6. The composition of claim 1, wherein the polymeric carrier matrix further comprises silicon dioxide.

25. The composition of claim 1, wherein said uniformity of the film is maintained by preventing surface skinning prior to drying the depth of said film using a conventional drying method.

26. The composition of claim 25, wherein said uniformity of the film is maintained by using a viscosity that maintains a non-self-aggregating uniform heterogeneity of said film or prevents rippling.

7. A drug delivery composition for making a plurality of individual unit doses in a self-supporting film dosage form, which plurality of individual unit doses being cut from a self-supporting film not made in a mold or well having at least one particulate active substantially uniformly stationed in said film, each of said individual unit doses containing a desired amount of said at least one particulate active, said composition comprising:

a. a polymeric carrier matrix comprising a component selected from the group consisting of polyethylene oxide, polyvinylpyrrolidone, cellulose, a cellulose derivative, polyvinyl alcohol, a polysaccharide, and combinations thereof;

b. naloxone or a pharmaceutical salt thereof;

c. the at least one particulate active selected from the group consisting of analgesics, narcotics, opiates, and opiate derivatives;

d. a buffering agent;

e. an antioxidant;

f. an artificial sweetener;

g. at least one coloring agent selected from FD&

C colors, D&

C colors and combinations thereof; and

h. at least one flavor,

wherein said uniformity of the film from which the plurality of individual unit doses is cut is measured by substantially equally sized individual unit doses cut from the film which do not vary by more than 10% of a desired amount of said at least one particulate active and

wherein said uniformity of the film is maintained by preventing surface skinning prior to drying the depth of said film.

8. The composition of claim 7, wherein the antioxidant is selected from the group consisting of BHT, BHA, citric acid, propyl gallate, sodium sulfate, sodium metabisulfite, ascorbic acid, tocopherol, tocopherol ester derivatives, 2-mercaptobenzimidazole, and combinations thereof.

9. The composition of claim 7, wherein the at least one flavor comprises a lemon-lime flavor.

10. The composition of claim 7, wherein the at least one flavor comprises a component selected from the group consisting of alpha-citral, beta-citral, decanal, aldehyde C-8, aldehyde C-9, aldehyde C-12, and combinations thereof.

11. The composition of claim 7, further comprising shellac.

12. The composition of claim 7, wherein the polymeric carrier matrix further comprises silicon dioxide.

27. The composition of claim 7, wherein said uniformity of the film is maintained by preventing surface skinning prior to drying the depth of said film using a conventional drying method.

28. The composition of claim 27, wherein said uniformity of the film is maintained by using a viscosity that maintains a non-self-aggregating uniform heterogeneity of said film or prevents rippling.

13. A drug delivery composition for making a plurality of individual unit doses in a self-supporting film dosage form, which plurality of individual unit doses being cut from a self-supporting conveyed film having at least one particulate active substantially uniformly stationed in said conveyed film, each of said individual unit doses containing a desired amount of said at least one particulate active, said composition comprising:

a. a polymeric carrier matrix comprising polyethylene oxide and polyvinylpyrrolidone;

b. naloxone or a pharmaceutical salt thereof;

c. the at least one particulate active selected from the group consisting of analgesics, narcotics, opiates, and opiate derivatives;

d. citric acid;

e. an antioxidant;

f. a sweetener selected from the group consisting of acesulfame potassium salt, sodium saccharin, sucralose, aspartame and combinations thereof;

g. at least one coloring agent selected from the group consisting of FD&

C colors, D&

C colors, and combinations thereof;

h. at least one flavor;

i. a hydrogenated starch hydrolysate; and

j. disodium phosphate,

wherein said uniformity of the conveyed film from which the plurality of individual unit doses is cut is measured by substantially equally sized individual unit doses cut from the conveyed film which do not vary by more than 10% of a desired amount of said at least one particulate active.

14. The composition of claim 13, further comprising propylene glycol, shellac, or a combination thereof.

15. The composition of claim 13, wherein the antioxidant is selected from the group consisting of BHT, BHA, citric acid, propyl gallate, sodium sulfate, sodium metabisulfite, ascorbic acid, tocopherol, tocopherol ester derivatives, 2-mercaptobenzimidazole, and combinations thereof.

16. The composition of claim 13, wherein the at least one flavor comprises a lemon-lime flavor.

17. The composition of claim 13, wherein the at least one flavor comprises a component selected from the group consisting of alpha-citral, beta-citral, decanal, aldehyde C-8, aldehyde C-9, aldehyde C-12, and combinations thereof.

18. The composition of claim 13, wherein the polymeric carrier matrix further comprises silicon dioxide.

29. The composition of claim 13, wherein said uniformity of the film is maintained by preventing surface skinning prior to drying the depth of said film using a conventional drying method.

19. A drug delivery composition for making a plurality of individual unit doses in a self-supporting film dosage form, which plurality of individual unit doses being cut from a self-supporting film having at least one particulate active substantially uniformly stationed in said film, each of said individual unit doses containing a desired amount of said at least one particulate active, said composition comprising:

a. a polymeric carrier matrix comprising a component selected from the group consisting of polyethylene oxide, polyvinylpyrrolidone, cellulose, a cellulose derivative, polyvinyl alcohol, a polysaccharide, and combinations thereof;

b. naloxone or a pharmaceutical salt thereof;

c. the at least one particulate active selected from the group consisting of analgesics, narcotics, opiates, and opiate derivatives;

d. a buffering agent;

e. an antioxidant;

f. an artificial sweetener;

g. at least one coloring agent selected from FD&

C colors, D&

C colors and combinations thereof; and

h. at least one flavor,

wherein said uniformity of the film from which the plurality of individual unit doses is cut is measured by substantially equally sized individual unit doses cut from the film which do not vary by more than 10% of a desired amount of said at least one particulate active.

20. The composition of claim 19, wherein the antioxidant is selected from the group consisting of BHT, BHA, citric acid, propyl gallate, sodium sulfate, sodium metabisulfite, ascorbic acid, tocopherol, tocopherol ester derivatives, 2-mercaptobenzimidazole, and combinations thereof.

21. The composition of claim 19, wherein the at least one flavor comprises a lemon-lime flavor.

22. The composition of claim 19, wherein the at least one flavor comprises a component selected from the group consisting of alpha-citral, beta-citral, decanal, aldehyde C-8, aldehyde C-9, aldehyde C-12, and combinations thereof.

23. The composition of claim 19, further comprising shellac.

24. The composition of claim 19, wherein the polymeric carrier matrix further comprises silicon dioxide.

30. The composition of claim 19, wherein said uniformity of the film is maintained by preventing surface skinning prior to drying the depth of said film using a conventional drying method.