Pharmaceutical composition comprising licarbazepine acetate

• US 10,912,781 B2
• Filed: 01/04/2017
• Issued: 02/09/2021
• Est. Priority Date: 10/26/2007
• Status: Active Grant

• Current Assignee: BIAL Portela & Ca, SA
• Original Assignee: BIAL Portela & Ca, SA
• Inventors: Cardoso de Vasconcelos, Teofilo, dos Santos Lima, Ricardo Jorge, Cerdeira de Campos Costa, Rui
• Primary Examiner(s): Barham, Bethany P
• Assistant Examiner(s): Anthopolos, Peter
• Application Number:
  US15/397,945
• Publication Number:
  US 20170112850A1
• Time in Patent Office: 1,497 Days
• Field of Search: None
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1682 Processes
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A pharmaceutical composition comprising licarbazepine acetate, especially eslicarbazepine acetate, in combination with suitable excipients, in particular a binder, and a disintegrant. Also disclosed is a granulation process, especially a wet granulation process, for making the pharmaceutical composition.

Claims

1. A pharmaceutical composition consisting essentially of eslicarbazepine acetate in combination with a binder and a disintegrant, wherein eslicarbazepine acetate is present in an amount of from 80 to 90 wt %, the binder is present in an amount of from 3 to 10 wt %, and the disintegrant is present in an amount of from 3 to 10 wt %, and wherein the pharmaceutical composition exhibits a dissolution of at least 60% at about 30 minutes at a temperature of 37±

0.5°

C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm.

2. The pharmaceutical composition of claim 1, wherein the binder is povidone, which is present in an amount of from 5 to 9 wt %.

3. The pharmaceutical composition of claim 1, wherein the binder is povidone, hypromellose, hydroxypropyl cellulose, methyl-cellulose, pregelatinized maize starch or gelatine, or a mixture of one or more thereof.

4. The pharmaceutical composition of claim 3, wherein the binder is povidone.

5. The pharmaceutical composition of claim 1, wherein the disintegrant is croscarmellose sodium, which is present in an amount of from 5 to 8 wt %.

6. The pharmaceutical composition of claim 1, wherein the disintegrant is croscarmellose sodium, crospovidone, low substituted hydroxypropyl cellulose, microcrystalline cellulose, carboxymethyl cellulose sodium, carboxymethylcellulose calcium, sodium starch glycolate, or a mixture of one or more thereof.

7. The pharmaceutical composition of claim 6, wherein the disintegrant is croscarmellose sodium.

8. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is prepared by a wet granulation process and comprises granules of eslicarbazepine acetate.

9. The pharmaceutical composition of claim 8, wherein the disintegrant is intragranular or extragranular.

10. The pharmaceutical composition of claim 8, wherein at least part of the disintegrant is intragranular and at least part of the disintegrant is extragranular.

11. The pharmaceutical composition of claim 10, wherein from about 20 to about 80 wt % of the total amount of the disintegrant is present in the granules.

12. The pharmaceutical composition of claim 10, wherein from about 30 to about 70 wt % of the total amount of the disintegrant is present in the granules.

13. The pharmaceutical composition of claim 10, wherein from about 40 to about 60 wt % of the total amount of the disintegrant is in the granules.

14. The pharmaceutical composition of claim 10, wherein from about 45 to about 55 wt % of the total amount of the disintegrant is in the granules.

15. The pharmaceutical composition of claim 10, wherein about 50 wt % of the total amount of the disintegrant is in the granules.

16. The pharmaceutical composition of claim 10, wherein:

eslicarbazepine acetate is present in the intragranular phase;

the binder is povidone, which is present in an amount of from 5 to 9 wt %; and

the disintegrant is croscarmellose sodium, which is present in an amount of from 5 to 8 wt %, and wherein about 50% of croscarmellose sodium is present in the intragranular phase and about 50% of croscarmellose sodium is present in the extragranular phase.

17. The pharmaceutical composition of claim 1, further comprising a lubricant, and/or a glidant.

18. The pharmaceutical composition of claim 1, further comprising a lubricant, which is magnesium stearate and is present in an amount of from about 0.1 to about 3 wt %.

19. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition does not comprise a calcium carbonate, calcium phosphate dibasic anhydrous, calcium phosphate dibasic dihydrate, calcium phosphate tribasic, or calcium sulphate.

20. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is in an oral dosage form.

21. The pharmaceutical composition of claim 20, wherein the oral dosage form is a tablet or capsule.

22. A pharmaceutical composition consisting essentially of (i) from 80 to 90 wt % eslicarbazepine acetate, (ii) from 3 to 10 wt % povidone, and (iii) from 3 to 10 wt % croscarmellose sodium, wherein the pharmaceutical composition exhibits a dissolution of at least 60% at about 30 minutes at a temperature of 37±

0.5°

C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm.

23. A pharmaceutical composition consisting essentially of (i) from 80 to 90 wt % eslicarbazepine acetate, (ii) from 3 to 10 wt % povidone, and (iii) from 3 to 10 wt % croscarmellose sodium, wherein the pharmaceutical composition is prepared by a wet granulation process and comprises granules of eslicarbazepine acetate, and wherein the pharmaceutical composition exhibits a dissolution of at least 60% at about 30 minutes at a temperature of 37±

0.5°

C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm.

24. A pharmaceutical composition consisting essentially of (i) from 80 to 90 wt % eslicarbazepine acetate, (ii) from 3 to 10 wt % povidone, and (iii) from 3 to 10 wt % croscarmellose sodium, wherein the pharmaceutical composition has an apparent density of from about 0.5 to about 1.5 g/mL, and wherein the pharmaceutical composition exhibits a dissolution of at least 60% at about 30 minutes at a temperature of 37±

0.5°

C. and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm.

25. The pharmaceutical composition of claim 24, wherein the pharmaceutical composition is in an oral dosage form.