FORMULATIONS CONTAINING NALBUPHINE AND USES THEREOF

• US 20160271124A1
• Filed: 06/01/2016
• Published: 09/22/2016
• Est. Priority Date: 08/20/2010
• Status: Active Grant

• Current Assignee: Debregeas ET Associes Pharma
• Original Assignee: Debregeas ET Associes Pharma
• Inventors: LEBON, Christophe, PAUL, David Olivier, SUPLIE, Pascal
• Granted Patent: US 10,441,585 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• 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 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 with drug-free core
• 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 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Immediate release, oral, pharmaceutical formulation comprising nalbuphine or a pharmaceutically acceptable salt thereof, and at least one hydrophilic granulation carrier, one hydrophilic binder and one lubricant.

Claims

1. An immediate release, oral pharmaceutical formulation comprising:

nalbuphine or a pharmaceutically acceptable salt thereof;

at least one hydrophilic granulation carrier;

at least one hydrophilic binder, and

at least one lubricant,

wherein the pharmaceutical formulation does not include a compound capable of sustaining the release of the nalbuphine.

2. The pharmaceutical formulation of claim 1, wherein:

the nalbuphine is from 1.99 to 30% by weight relative to a total weight of the formulation,

the at least one hydrophilic granulation carrier is from 45 to 70% by weight relative to a total weight of the formulation,

the at least one hydrophilic binder is from 2 to 10% by weight relative to a total weight of the formulation, and

the at least one lubricant is from 0.5 to 7% by weight relative to a total weight of the formulation.

3. The pharmaceutical formulation of claim 1, wherein

the at least one hydrophilic granulation carrier is selected from the group consisting of mannitol, sorbitol, maltitol, xylitol, lactose, dicalcium phosphate, calcium carbonate, potassium carbonate, magnesium carbonate, sodium carbonate, a gluconate, magnesium aluminium silicate, sugar crystals, starch derivatives, microcrystalline cellulose, saccharose, α

-lactose monohydrate, polyvinyl pyrrolidone (PVP) or a derivative thereof, methylcellulose, hydroxypropyl methylcellulose, carboxy-methylcellulose, and polyethylene glycol.

4. The pharmaceutical formulation of claim 3, wherein

the at least one hydrophilic granulation carrier is selected from the group consisting of mannitol, microcrystalline cellulose, α

-lactose monohydrate, magnesium aluminium silicate, polyvinyl pyrrolidone or a derivative thereof, and polyethylene glycol.

5. The pharmaceutical formulation of claim 1, wherein

the hydrophilic binder is selected from the group consisting of polyvinyl pyrrolidone or a derivative thereof, a polyol, lactose, a cellulose derivative, polyethylene glycol or a derivative thereof, gums and carbomers.

6. The pharmaceutical formulation of claim 1, wherein

the lubricant is selected from the group consisting of silicon dioxide, magnesium stearate, anhydrous colloidal silica, sodium stearyl fumarate and talcum.

7. The pharmaceutical formulation of claim 2, wherein

the nalbuphine is from 1.99 to 4.69% by weight relative to a total weight of the formulation.

8. The pharmaceutical formulation of claim 1, wherein

wherein the formulation is in a form of an uncoated tablet.

9. The pharmaceutical formulation of claim 8, wherein

the tablet has a total weight in a range from 147.75 mg to 640 mg.

10. The pharmaceutical formulation of claim 8, wherein

the tablet has a total weight in a range from 251.09 mg to 640 mg.

11. The pharmaceutical formulation of claim 1, wherein

a total amount of the granulation carrier in the tablet is in a range of 60.48 mg to 349.49 mg.

12. The pharmaceutical formulation of claim 11, wherein

the total amount of the granulation carrier in the tablet is in a range of 246.71 mg to 349.49 mg.

21. The pharmaceutical formulation of claim 8, wherein

the tablet has a total weight in a range from 147.75 mg to 640 mg.

22. The pharmaceutical formulation of claim 8, wherein

the tablet has a total weight in a range from 251.09 mg to 640 mg.

27. The pharmaceutical formulation of claim 1, wherein the nalbuphine has a bioavailability in a range of from 31.80 ng/ml·

hr to 38.1 ng/ml·

hr.

13. An immediate release, oral pharmaceutical formulation comprising:

nalbuphine or a pharmaceutically acceptable salt thereof;

at least one hydrophilic granulation carrier,

at least one hydrophilic binder, and

at least one lubricant,

wherein at least 75% of the active ingredient is released in 45 minutes when the formulation is subjected to constant agitation by an impeller at 50 rpm in a vessel containing 500 ml purified water and held at 37°

C.

14. The pharmaceutical formulation of claim 13, wherein:

the nalbuphine is from 1.99 to 30% by weight relative to a total weight of the formulation,

the at least one hydrophilic granulation carrier is from 45 to 70% by weight relative to a total weight of the formulation,

the at least one hydrophilic binder is from 2 to 10% by weight relative to a total weight of the formulation, and

the at least one lubricant is from 0.5 to 7% by weight relative to a total weight of the formulation.

15. The pharmaceutical formulation of claim 13, wherein

the at least one hydrophilic granulation carrier is selected from the group consisting of mannitol, sorbitol, maltitol, xylitol, lactose, dicalcium phosphate, calcium carbonate, potassium carbonate, magnesium carbonate, sodium carbonate, a gluconate, magnesium aluminium silicate, sugar crystals, starch derivatives, microcrystalline cellulose, saccharose, α

-lactose monohydrate, polyvinyl pyrrolidone (PVP) or a derivative thereof, methylcellulose, hydroxypropyl methylcellulose, carboxy-methylcellulose, and polyethylene glycol.

16. The pharmaceutical formulation of claim 15, wherein

the at least one hydrophilic granulation carrier is selected from the group consisting of mannitol, microcrystalline cellulose, α

-lactose monohydrate, magnesium aluminium silicate, polyvinyl pyrrolidone or a derivative thereof, and polyethylene glycol.

17. The pharmaceutical formulation of claim 13, wherein

the hydrophilic binder is selected from the group consisting of polyvinyl pyrrolidone or a derivative thereof, a polyol, lactose, a cellulose derivative, polyethylene glycol or a derivative thereof, gums and carbomers.

18. The pharmaceutical formulation of claim 13, wherein

the lubricant is selected from the group consisting of silicon dioxide, magnesium stearate, anhydrous colloidal silica, sodium stearyl fumarate and talcum.

19. The pharmaceutical formulation of claim 14, wherein

the nalbuphine is from 1.99 to 4.69% by weight relative to a total weight of the formulation.

20. The pharmaceutical formulation of claim 13, wherein

wherein the formulation is in a form of an uncoated tablet.

23. The pharmaceutical formulation of claim 13, wherein

a total amount of the granulation carrier in the tablet is in a range of 60.48 mg to 349.49 mg.

24. The pharmaceutical formulation of claim 23, wherein

the total amount of the granulation carrier in the tablet is in a range of 246.71 mg to 349.49 mg.

25. The pharmaceutical formulation of claim 13, wherein

more than 80% of the active ingredient is released in 45 minutes when the formulation is subjected to constant agitation by an impeller at 50 rpm in a vessel containing 500 ml purified water and held at 37°

C.

26. The pharmaceutical formulation of claim 13, wherein

at least 93% of the active ingredient is released in 15 minutes when the formulation is subjected to constant agitation by an impeller at 50 rpm in a vessel containing 500 ml purified water and held at 37°

C.

28. The pharmaceutical formulation of claim 13, wherein the nalbuphine has a bioavailability in a range of from 31.80 ng/ml·

hr to 38.1 ng/ml·

hr.