Compositions of GLP-1 peptides and preparation thereof
The invention relates to pharmaceutical compositions comprising a first type of granules and a second type of granules, wherein said first type of granules comprises a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and no GLP-1 peptide, and wherein said second type of granules comprises a GLP-1 peptide and no salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, as well as the intermediate granules, processes for the preparation of the granules and compositions, and use thereof in medicine.
1. A solid dosage pharmaceutical composition comprising:
(a) a first type of granules comprising sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid (SNAC), lubricant, and no GLP-1 peptide, wherein the SNAC is at least 75% (w/w), and wherein the lubricant is less than 10% (w/w);
(b) a second type of granules comprising GLP-1 peptide, filler, binder, and no SNAC, wherein the GLP-1 peptide is 2 to 40% (w/w), wherein the filler is at least 15% (w/w), and wherein the binder is less than 40% (w/w); wherein:
the GLP-1 peptide is semaglutide, wherein the formula of semaglutide is N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)butyrylamino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl] [Aib8,Arg34]GLP-1(7-37); and
the composition is a tablet, wherein the weight of the tablet is in the range of 150 mg to 1000 mg.
2. The pharmaceutical composition according to claim 1 , wherein the release of said sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid is faster than the release of said GLP-1 peptide in the first 20 minutes of dissolution as determined by dissolution testing using Assay (I) carried out at pH 2.5.
3. The pharmaceutical composition according to claim 1 , wherein the first type of granules further comprises filler, wherein the filler is less than 20% (w/w).
4. The pharmaceutical composition according to claim 1 or claim 3 , wherein the composition comprises at least 60% (w/w) of SNAC, less than 10% (w/w) binder, 5-40% (w/w) filler, and less than 10% (w/w) lubricant.
5. The pharmaceutical composition according to claim 1 or claim 3 , wherein the binder is povidone.
6. The solid dosage pharmaceutical composition according to claim 1 or claim 3 , wherein the filler is microcrystalline cellulose.
7. The solid dosage pharmaceutical composition according to claim 1 or claim 3 , wherein the lubricant is magnesium stearate.
8. The pharmaceutical composition according to claim 1 or claim 3 wherein the weight of the tablet is in the range of 300 mg to 600 mg.
9. The solid dosage pharmaceutical composition according to claim 1 or claim 3 , wherein the weight of the tablet is in the range of 350 mg to 450 mg.
10. A solid dosage pharmaceutical composition comprising:
(a) a first type of granule comprising sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid (SNAC), lubricant, and no GLP-1 peptide, wherein the SNAC is at least 75% (w/w), and wherein the lubricant is less than 10% (w/w);
(b) a second type of granule comprising GLP-1 peptide, filler, binder, and no SNAC, wherein the GLP-1 peptide is 2 to 40% (w/w), the filler is at least 15% (w/w), and the binder is less than 40% (w/w);
wherein the GLP-1 peptide is semaglutide, and wherein the formula of semaglutide is N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino) butyrylamino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl] [Aib8,Arg34]GLP-1(7-37).
11. The pharmaceutical composition according to claim 10 , wherein the filler is microcrystalline cellulose, the lubricant is magnesium stearate, and the binder is povidone.
12. The pharmaceutical composition according to claim 10 , wherein the first type of granules further comprises filler, wherein the filler is less than 20% (w/w).
13. The pharmaceutical composition according to claim 12 , wherein the filler of the first type of granules is microcrystalline cellulose, wherein the filler of the second type of granules is microcrystalline cellulose, wherein the lubricant is magnesium stearate, and wherein the binder is povidone.
14. The pharmaceutical composition according to claim 13 , wherein the composition is in the form of a tablet having a weight in a range of 150 mg to 1000 mg.
15. The pharmaceutical composition according to claim 14 , wherein the weight of the tablet is in the range of 300 mg to 600 mg.
16. The pharmaceutical composition according to claim 15 , wherein the weight of the tablet is in the range of 350 mg to 450 mg.
17. A solid dosage pharmaceutical composition comprising:
(a) a first type of granules consisting essentially of sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid (SNAC) and one or more excipients selected from the group consisting of a lubricant, a filler, and a binder, wherein the SNAC is at least 75% (w/w);
(b) a second type of granules consisting essentially of GLP-1 peptide and one or more excipients selected from the group consisting of a lubricant, a filler, and a binder, wherein the GLP-1 peptide is 2 to 40% (w/w);
wherein the GLP-1 peptide is semaglutide, and wherein the formula of semaglutide is N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)butyrylamino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl] [Aib8,Arg34]GLP-1(7-37).
18. The pharmaceutical composition according to claim 17 , wherein the composition is a tablet with a weight in the range of 150 mg to 1000 mg.
19. The pharmaceutical composition according to claim 18 , wherein the weight of the tablet is in the range of 300 mg to 600 mg.
20. The pharmaceutical composition according to claim 19 , wherein the weight of the tablet is in the range of 350 mg to 450 mg.
21. The pharmaceutical composition according to claim 17 , wherein (a) the first type of granules consists essentially of (SNAC) and the lubricant; and wherein (b) the second type of granules consists essentially of semaglutide, the filler, and the binder.
22. The pharmaceutical composition according to claim 21 , wherein the lubricant of the first type of granules is magnesium stearate, wherein the filler of the second type of granules is microcrystalline cellulose, and wherein the binder of the second type of granules is povidone.
23. The pharmaceutical composition according to claim 17 , wherein (a) the first type of granules consists essentially of (SNAC), the lubricant, and the filler; and wherein (b) the second type of granules consists essentially of semaglutide, the filler, and the binder.
24. The pharmaceutical composition according to claim 23 , wherein the lubricant of the first type of granules is less than 10% (w/w), wherein the filler of the first type of granules is less than 20% (w/w), wherein the filler of the second type of granules is at least 15% (w/w), and wherein the binder of the second type of granules is less than 40% (w/w).
25. The pharmaceutical composition according to claim 24 , wherein the lubricant of the first type of granules is magnesium stearate, wherein the filler of the first type of granules is microcrystalline cellulose, wherein the filler of the second type of granules is microcrystalline cellulose, and wherein the binder of the second type of granules is povidone.
26. The pharmaceutical composition according to claim 25 , wherein the composition is a tablet with a weight in a range of 150 mg to 1000 mg.
27. The pharmaceutical composition according to claim 26 , wherein the weight of the tablet is in the range of 300 mg to 600 mg.
28. The pharmaceutical composition according to claim 27 , wherein the weight of the tablet is in the range of 350 mg to 450 mg.