Film-like form of administration for the transmucosal delivery of antidiabetic peptides

Patent metadata

Field	Value
Publication number	US-11213491-B2
Application number	US-201716094933-A
Country	US
Kind code	B2
Filing date	Apr 20, 2017
Priority date	Apr 26, 2016
Publication date	Jan 4, 2022
Grant date	Jan 4, 2022

Abstract

The invention relates to film-like forms of administration for the transmucosal delivery of antidiabetic peptides via the oral mucosa and to processes for the production thereof. Antidiabetic peptides refers to peptides which are an active compound for the treatment of diabetes mellitus, and includes insulins, insulin analogs, incretins and incretin mimetics.

First claim

The invention claimed is:

1. A transmucosal film dosage form for the delivery of an antidiabetic peptide via the oral mucosa, comprising an active-compound-containing layer, said active-compound-containing layer comprising (i) at least one antidiabetic peptide and (ii) matrix polymer consisting of a mixture of at least two hydroxypropylmethylcelluloses of different viscosity within the active-compound-containing layer,
wherein the film dosage form residence time on the oral mucosa is from 30 minutes to 1 hour.

2. The film dosage form as claimed in claim 1 , wherein the mixture of hydroxypropylmethylcelluloses is a mixture of a first hydroxypropylmethylcellulose, a second hydroxypropylmethylcellulose, and a third hydroxypropylmethylcellulose, in which the first hydroxypropylmethylcellulose is a hydroxypropylmethylcellulose of high viscosity, the second hydroxypropylmethylcellulose is a hydroxypropylmethylcellulose of medium viscosity, and the third hydroxypropylmethylcellulose is a hydroxypropylmethylcellulose of low viscosity.

3. The film dosage form as claimed in claim 2 , wherein the hydroxypropylmethylcellulose of high viscosity has a viscosity of approximately 3,000 mPa·s to approximately 5,600 mPa, based upon a 2% solution in water at a temperature of 20° C. on a Brookfield LV viscometer.

4. The film dosage form as claimed in claim 3 , wherein the hydroxypropylmethylcellulose of medium viscosity has a viscosity of approximately 75 mPa·s to approximately 140 mPa·s, based upon a 2% solution in water at a temperature of 20° C. on a Brookfield LV viscometer and
the film dosage form includes a single active-compound-containing layer.

5. The film dosage form as claimed in claim 2 , wherein the hydroxypropylmethylcellulose of low viscosity has a viscosity of approximately 3 mPa·s, based upon a 2% solution in water at a temperature of 20° C. on a Brookfield LV viscometer.

6. The film dosage form as claimed in claim 1 , wherein the at least one antidiabetic peptide is selected from the group consisting of insulins, insulin analogs, incretins, and incretin mimetics.

7. The film dosage form as claimed in claim 1 , further having a cover layer.

8. The film dosage form as claimed in claim 7 , wherein the cover layer comprises ethylcellulose and the ethylcellulose content in the cover layer is at least 50 wt %, but at most 99 wt %, based on the total weight of the cover layer.

9. A method for the production of the film dosage form for the transmucosal delivery of an antidiabetic peptide as claimed in claim 1 , comprising the following steps:
dissolving and/or suspending components of the active-compound-containing layer in a solvent, thereby forming a solution or suspension,
applying the solution or suspension to a carrier in a specified thickness; and
subsequent drying.

10. The method as claimed in claim 9 , further comprising
dissolving and/or suspending components of a cover layer in a solvent,
applying the solution or suspension for the cover layer to a carrier, and
subsequent drying of the cover layer.

11. The method as claimed in claim 10 , wherein the solvent for dissolving or suspending the components of the active-compound-containing layer and/or the components of the cover layer is selected from the group comprising water and mixtures of water and ethanol.

12. The method as claimed in claim 9 , wherein the drying is carried out at a temperature of not more than 80° C.

13. The method as claimed in claim 9 , wherein the step of applying the solution or suspension with the components of the active-compound-containing layer is carried out on a prefabricated active-compound-containing layer or a prefabricated cover layer.

14. The method as claimed in claim 9 , further comprising separating the film dosage form or cutting the film dosage form into strips of predetermined width and length; and subsequent packaging.

15. The film dosage form as claimed in claim 7 , wherein the cover layer comprises ethylcellulose.

16. The film dosage form as claimed in claim 8 , wherein the content of ethylcellulose in the cover layer is at least 55 wt %, but at most 95 wt %, based on the total weight of the cover layer.

17. The film dosage form as claimed in claim 8 , wherein the content of ethylcellulose in the cover layer is at least 60 wt %, but at most 94 wt %, based on the total weight of the cover layer.

18. The film dosage form as claimed in claim 8 , wherein the content of ethylcellulose in the cover layer is at least 65 wt %, but at most 93.5 wt %, based on the total weight of the cover layer.

19. The method as claimed in claim 11 , wherein the solvent is a mixture of water and ethanol in a ratio of approximately 80 vol %:20 vol % or a mixture of water and ethanol in a ratio of approximately 4 vol %:96 vol %.

20. The method as claimed in claim 12 , wherein the drying is carried out at a temperature of not more than 50° C.

21. A film dosage form for the delivery of an antidiabetic peptide via the oral mucosa, comprising an active-compound-containing layer, said active-compound-containing layer comprising (i) at least one antidiabetic peptide and (ii) matrix polymer consisting of a mixture of at least two hydroxypropylmethylcelluloses of different viscosity, wherein said mixture comprises a hydrodroxypropylmethylcellulose having a viscosity of approximately 3,000 mPa·s to approximately 5,600 mPa·s,
wherein the film dosage form residence time on the oral mucosa is from 30 minutes to 1 hour.

22. The film dosage form as claimed in claim 2 , wherein the hydroxypropylmethylcelluloses are present in a weight ratio of 1:6 to 10:4.07 to 6 based on first hydroxypropylmethylcellulose:second hydroxypropylmethylcellulose:third hydroxypropylmethylcellulose.

23. The film dosage form as claimed in claim 1 , wherein said film dosage form comprises permeability enhancer.

24. A transmucosal film dosage form for the delivery of an antidiabetic peptide comprising an active-compound-containing layer, said active-compound-containing layer comprising at least one antidiabetic peptide and matrix polymer consisting of a mixture of three hydroxypropylmethylcelluloses of different viscosities, wherein said film dosage form comprises at least 12 wt % antidiabetic peptide,
wherein the film dosage form residence time on the oral mucosa is from 30 minutes to 1 hour.

25. A transmucosal film dosage form as claimed in claim 24 , wherein said film dosage form comprises at least 15 wt % antidiabetic peptide.

26. A transmucosal film dosage form for the delivery of an antidiabetic peptide via the oral mucosa, comprising at least one active-compound-containing layer, said at least one active-compound-containing layer comprising (i) at least one antidiabetic peptide and (ii) matrix polymer consisting of a mixture of three hydroxypropylmethylcelluloses of different viscosity within the active-compound-containing layer,
wherein the first hydroxypropylmethylcellulose has a viscosity of approximately 3,000 mPa·s to approximately 5,600 mPa·s, based upon a 2% solution in water at a temperature of 20° C. on a Brookfield LV viscometer
the second hydroxypropylmethylcellulose has a viscosity of approximately 75 mPa·s to approximately 140 mPa·s, based upon a 2% solution in water at a temperature of 20° C. on a Brookfield LV viscometer; and
the third hydroxypropylmethylcellulose has a viscosity of approximately 3 mPa·s, based upon a 2% solution in water at a t

Assignees

• Lts Lohmann Therapie Systeme Ag

Inventors

• Müller Markus
• Hammes Claudia Maria
• Schmitz Christoph
• Linn Michael
• Sameti Mohammad
• Klaffenbach Peter

Classifications

• A61K38/28 Primary

  Insulins · CPC title

• A61K38/26

  Glucagons · CPC title

• A61K9/006

  Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K47/38

  Cellulose; Derivatives thereof · CPC title