Tablet formulation comprising a GLP-1 peptide and a delivery agent

Patent metadata

Field	Value
Publication number	US-11033499-B2
Application number	US-201815958236-A
Country	US
Kind code	B2
Filing date	Apr 20, 2018
Priority date	Jun 20, 2012
Publication date	Jun 15, 2021
Grant date	Jun 15, 2021

Abstract

The present invention relates to solid compositions comprising a GLP-1 peptide and a delivery agent, such as SNAC, as well as uses thereof.

First claim

The invention claimed is:

1. A tablet comprising a granulate, wherein said granulate comprises: i) no more than 15% (w/w) GLP-1 peptide, wherein the GLP-1 peptide is a peptide; and ii) at least 50% (w/w) salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid (NAC); wherein said tablet has
a) a bulk density of at least 1.0 g/cm 3 ;
b) a median pore diameter of no more than 1.5 μm; and
c) a feature selected from the group consisting of a maximum pore diameter of no more than 4 μm, a crushing strength of 50-400 N, and a disintegration time of 22 minutes or less.

2. The tablet according to claim 1 , wherein the GLP-1 peptide comprises a substituent comprising a fatty acid or a fatty diacid, of formula (X)

wherein n is at least 13;
and wherein said peptide optionally comprises one or more 8-amino-3,6-dioxaoctanoic acid (OEG).

3. The tablet according to claim 1 , wherein the GLP-1 peptide is semaglutide.

4. The tablet according to claim 1 , wherein the salt of NAC is monosodium NAC (SNAC).

5. The tablet according to claim 1 , wherein the amount of the salt of NAC is 50-90% (w/w).

6. The tablet according to claim 1 , wherein the tablet comprises an intragranular and an extragranular part, and wherein the extragranular part comprises a lubricant.

7. The tablet according to claim 1 , wherein the granulate comprises
i) 1-15% (w/w) GLP-1 peptide,
ii) 55-85% (w/w) salt of NAC, and
iii) 1-20% (w/w) binder; and wherein the tablet further comprises 10-35% (w/w) filler and 0.5-3% (w/w) lubricant.

8. The tablet according to claim 1 , wherein the tablet does not comprise a superdisintegrant.

9. The tablet according to claim 1 , wherein the tablet is for oral administration.

10. The tablet according to claim 1 , wherein the tablet is prepared by exerting a compression force in the range of 2-25 kN.

11. A method of treating type 2 diabetes or obesity comprising administering to a subject in need of such treatment a tablet according to claim 1 .

12. The tablet according to claim 4 , wherein the SNAC is anhydrous SNAC monosodium salt.

13. The tablet according to claim 6 , wherein the extragranular part further comprises a filler.

14. The tablet according to claim 1 , wherein said granulate comprises: i) no more than 15% (w/w) GLP-1 peptide, wherein the GLP-1 peptide is a peptide and ii) at least 50% (w/w) salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid (NAC); wherein said tablet has
a) a bulk density of at least 1.0 g/cm 3 ;
b) a median pore diameter of no more than 1.5 μm; and
c) a maximum pore diameter of no more than 4 μm.

15. The tablet according to claim 1 , wherein said granulate comprises: i) no more than 15% (w/w) GLP-1 peptide, and ii) at least 50% (w/w) salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid (NAC); wherein said tablet has
a) a bulk density of at least 1.0 g/cm 3 ;
b) a median pore diameter of no more than 1.5 μm; and
c) a crushing strength of 50-400 N.

16. The tablet according to claim 1 , wherein said granulate comprises: i) no more than 15% (w/w) GLP-1 peptide, and ii) at least 50% (w/w) salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid (NAC); wherein said tablet has
a) a bulk density of at least 1.0 g/cm 3 ;
b) a median pore diameter of no more than 1.5 μm; and
c) a disintegration time of 22 minutes or less.

Assignees

• Novo Nordisk As

Inventors

• Jensen Simon Bjerregaard
• Sauerberg Per
• Nielsen Flemming S
• Pedersen Betty L
• Skibsted Erik

Classifications

• A61K38/26 Primary

  Glucagons · CPC title

• A61K9/2077

  Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K9/1617

  Organic compounds, e.g. phospholipids, fats · CPC title

• A61K9/2095

  Tabletting processes · CPC title