Modified release formulation of lacosamide

Patent metadata

Field	Value
Publication number	US-10786464-B2
Application number	US-201013505990-A
Country	US
Kind code	B2
Filing date	Nov 3, 2010
Priority date	Nov 3, 2009
Publication date	Sep 29, 2020
Grant date	Sep 29, 2020

Abstract

The present invention provides a modified release formulation of lacosamide. The modified release formulation of the present invention comprising lacosamide and modified release polymer provides modified release of lacosamide with minimal Cmax to Cmin peak to trough variation over a period of at least 12 hrs.

First claim

The invention claimed is:

1. A once daily modified release formulation comprising lacosamide as only active ingredient and at least two release modifying polymers, wherein the modified release formulation releases
a. not more than about 25% of lacosamide within 1 hour,
b. from about 30% to about 70% of lacosamide within 4 hours, and
c. not less than about 75% of lacosamide within 12 hours
when measured in USP type I dissolution apparatus, in 900 mL of 0.1 N HCl at 100 rpm, wherein lacosamide is present in an amount of about 13% to about 33% relative to the total weight of the formulation, and the at least two release modifying polymers are present in an amount of about 12% to about 52% relative to the total weight of the formulation and is selected from the group consisting of hydroxypropyl methylcellulose, polyethylene oxide, polyvinylpyrrolidone, ethyl cellulose, copolymers of vinyl pyrrolidone, an alginic acid derivative, hydrogenated vegetable oil and a combination thereof, and wherein the modified release formulation is in tablet or capsule form.

2. The once daily modified release formulation of claim 1 , wherein the at least two release modifying polymers are hydroxypropyl methylcellulose is present in an amount of about 28% relative to the total weight of the formulation and the copolymers of vinyl pyrrolidone is present in an amount of about 24% relative to the total weight of the formulation, and wherein the copolymers of vinyl pyrrolidone is copovidone.

3. The oral daily modified release formulation of claim 1 , wherein the at least two release modifying polymers are hydroxypropyl methylcellulose is present in an amount of about 7% relative to the total weight of the formulation and ethyl cellulose is present in an amount of about 27% relative to the total weight of the formulation.

4. The oral daily modified release formulation of claim 1 , wherein the at least two release modifying polymers are hydroxypropyl methylcellulose is present in an amount of about 8% relative to the total weight of the formulation and polyethylene oxide is present in an amount of about 24% relative to the total weight of the formulation.

5. The once daily modified release formulation of claim 1 , wherein a single dose comprises about 100 mg to 600 mg of lacosamide.

6. The once daily modified release formulation of claim 1 , wherein the modified release formulation comprises a core comprising lacosamide and a modified release coating.

7. The once daily modified release formulation of claim 1 , wherein the modified release formulation comprises:
(i) a core comprising non-pareil seed;
(ii) a coating disposed on the non-pareil seed with lacosamide; and
(iii) a modified release coating.

8. The once daily modified release formulation of claim 1 , wherein the modified release formulation comprises 100 mg to 600 mg of lacosamide; which when administered to a human subject provides an in-vivo plasma profile selected from:
(i) Mean T max of about 5 or more hours, or
(ii) Mean C max of less than about 4600 ng/ml, or
(iii) Mean AUC 0-72 of more than about 78500 ng·hr/ml.

9. The once daily modified release formulation of claim 1 , wherein the at least two release modifying polymers are hydroxypropyl methylcellulose is present in an amount of about 8% relative to the total weight of the formulation, polyethylene oxide is present in an amount of about 24% relative to the total weight of the formulation, and polyvinylpyrrolidone is present in an amount of about 4% relative to the total weight of the formulation of polyvinylpyrrolidone and the oral daily modified release formulation further comprising microcrystalline cellulose is present in an amount of about 28% relative to the total weight of the formulation.

10. The once daily modified release formulation of claim 1 , wherein the at least two release modifying polymers are hydroxypropyl methylcellulose is present in an amount of about 8% relative to the total weight of the formulation, polyvinylpyrrolidone is present in an amount of about 4% relative to the total weight of the formulation and an alginic acid derivative is present in an amount of about 24% relative to the total weight of the formulation, wherein the alginic acid derivative is sodium alginate.

11. The once daily modified release formulation of claim 1 , further comprising a diluent, and the diluent is present in an amount of about 23% to about 34% relative to the total weight of the formulation.

12. The once daily modified release formulation of claim 11 , wherein the diluent is microcrystalline cellulose.

13. The once daily modified release formulation of claim 12 , wherein the microcrystalline cellulose is present in an amount of about 23% to about 28% relative to the total weight of the formulation.

14. The once daily modified release formulation of claim 1 , further comprising a lubricant.

15. The once daily modified release formulation of claim 14 , wherein the lubricant comprises magnesium stearate.

16. The once daily modified release formulation of claim 1 , further comprising a glidant.

17. The once daily modified release formulation of claim 16 , wherein the glidant comprises colloidal silicon dioxide.

18. The once daily modified release formulation of claim 1 , wherein the copolymers of vinyl pyrrolidone polymer is copovidone.

19. The oral daily modified release formulation of claim 1 , wherein the at least two release modifying polymers are polyethylene glycol is present in an amount of about 17% relative to the total weight of the formulation, hydrogenated vegetable oil is present in an amount of about 8% relative to the total weight of the formulation, stearic acid is present in an amount of about 4% relative to the total weight of the formulation, and microcrystalline cellulose is present in the amount of about 34% relative to the total weight of the formulation.

20. The oral daily modified release formulation of claim 1 , wherein the at least two release modifying polymers are hydroxypropyl methylcellulose is present in an amount of about 28% relative to the total weight of the formulation and the copolymers of vinyl pyrrolidone polymer is present in an amount of about 24% relative to the total weight of the formulation, wherein the copolymers of vinyl pyrrolidone polymer is copovidone.

21. The oral daily modified release formulation of claim 1 , wherein the at least two release modifying polymers are hydroxypropyl methylcellulose is present in an amount of about 28% relative to the total weight of the formulation and microcrystalline cellulose is present in an amount of about 24% relative to the total weight of the formulation, and the copolymers of vinyl pyrrolidone polymer is present in an amount of about 24% relative to the total weight of the formulation, wherein the copolymers of vinyl pyrrolidone polymer is copovidone.

22. The once daily modified release formulation of claim 1 , further comprising about mannitol.

23. The once daily modified release formulation of claim 22 , wherein the mannitol is present in an amount of about 32% relative to the total weight of the formulation.

24. The once daily modified release formulation of claim 18 , wherein the copovidone is present in an amount of about 24% relative to the total weight of the formulation.

25. The once daily modified release formulation of claim 3 , further comprising sugar spheres/microcrystalline cellulose spheres in an amount of about 53% relat

Assignees

• Kulkarni Shirishkumar
• Dalal Satish Kumar
• Jahagirdar Harshal
• Konda Kishore Kumar
• Lupin Ltd

Inventors

• Kulkarni Shirishkumar
• Dalal Satish Kumar
• Jahagirdar Harshal
• Konda Kishore Kumar

Classifications

• A61K31/165

  having aromatic rings, e.g. colchicine, atenolol, progabide · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• A61K9/5078 Primary

  with drug-free core · CPC title

• A61K9/2077

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