GRANULE AND ORALLY DISINTEGRATING TABLET COMPRISING OXYCODONE

• US 20090304792A1
• Filed: 07/31/2007
• Published: 12/10/2009
• Est. Priority Date: 08/04/2006
• Status: Active Grant

• Current Assignee: ETHYPHARM
• Original Assignee: ETHYPHARM
• Inventors: Hoarau, Didier
• Granted Patent: US 8,465,776 B2
• Time in Patent Office: Days
• US Class Current: 424/465
• 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 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

The present invention relates to granules comprising oxycodone, as well as to orally disintegrating tablets including same and optionally acetaminophen.

Claims

1. Granule comprising a neutral core coated by:

(a) oxycodone or a pharmaceutically acceptable salt of oxycodone, and (b) at least a binding agent, said oxycodone coating being further coated by a subcoat comprising a compound soluble in gastric fluids, wherein said subcoat is further coated by a taste-masking coating comprising a polymer or copolymer with dialkylaminoalkyl(meth)acrylate units.

2. Granule according to claim 1, wherein the oxycodone comprises oxycodone hydrochloride.

3. Granule according to claim 1, wherein the compound soluble in gastric fluid and the binder are independently selected from the group consisting of:

cellulose-based polymers;

polyvinyl alcohols;

alginic acid or sodium alginate;

starch or pregelatinized starch;

sucroses and derivatives thereof;

guar gum;

polyethylene glycols; and

mixtures and copolymers thereof.

4. Granule according to claim 3, wherein the compound soluble in gastric fluid is a cellulose-based polymer selected from the group consisting of hydroxypropylmethylcellulose polymer, hydroxypropylcellulose polymer and hydroxyethylcellulose acrylic polymer.

5. Granule according to claim 1, wherein the polymer or copolymer with dialkylaminoalkyl(meth)acrylate units is a copolymer of dimethylaminoethyl methacrylate, methylmethacrylate and n-butyl methacrylate.

6. Granule according to claim 1, wherein the taste-masking coating also includes a pore-forming agent.

7. Granule according to claim 6, wherein the pore-forming agent is hydroxypropylmethylcellulose.

8. Process for the manufacture of granules according to claim 1, wherein a suspension of oxycodone in a hydroalcoholic medium is sprayed onto neutral cores.

20. Method for reducing pain in a patient, comprising oral administration to said patient of granules according to claim 1.

9. Orally disintegrating tablet comprising:

(a) granules comprising a neutral core coated by;

(a) oxycodone or a pharmaceutically acceptable salt of oxycodone, and (b) at least a binder, said oxycodone coating being further coated by a subcoat comprising a compound soluble in gastric fluid;

wherein said subcoat is further coated by a taste-masking coating comprising a polymer or copolymer with dialkylaminoalkyl(meth)acrylate units and optionally a pore-forming agent, and (b) at least one disintegrant and at least one diluent, wherein said disintegrant comprises crospovidone.

10. Orally disintegrating tablet according to claim 9, further comprising an anti-oxidant agent.

11. Orally disintegrating tablet according to claim 10, wherein the anti-oxidant agent is ascorbyl palmitate.

22. Method for reducing pain in a patient, comprising oral administration to said patient of a tablet according to claim 9.

12. Orally disintegrating tablets comprising:

(a) granules comprising a neutral core coated by;

(i) oxycodone or a pharmaceutically acceptable salt of oxycodone, and (ii) at least one binding agent, said oxycodone coating being further coated by a subcoat comprising a compound soluble in gastric fluid;

wherein said subcoat is further coated by a taste-masking coating comprising a polymer or copolymer with dialkylaminoalkyl(meth)acrylate units and optionally a pore-forming agent, (b) acetaminophen which is not included within said granules, and (c) at least one disintegrant and at least one soluble diluent agent, wherein said disintegrant comprises crospovidone.

13. Orally disintegrating tablet according to claim 12, wherein the compound soluble in gastric fluids is selected from the group consisting of:

cellulose-based polymers;

polyvinyl alcohols;

alginic acid or sodium alginate;

starch or pregelatinized starch;

sucroses and derivatives thereof;

guar gum;

polyethylene glycols, and mixtures and copolymers thereof.

14. Orally disintegrating tablet according to claim 13, wherein the compound soluble in gastric fluid is hydroxypropylmethylcellulose polymer, hydroxypropylcellulose polymer or hydroxyethylcellulose acrylic polymer.

15. Orally disintegrating tablet according to claim 12, further comprising an anti-oxidant agent.

16. Orally disintegrating tablet according to claim 15, wherein the anti-oxidant agent is ascorbyl palmitate.

17. Orally disintegrating tablet according to claim 12, wherein the pore-forming agent is hydroxypropylmethylcellulose.

18. Orally disintegrating tablet according to claim 12, comprising from 2.5 to 10 mg oxycodone and from 80 to 750 mg acetaminophen.

19. (canceled)

21. (canceled)

23. Process for manufacturing orally disintegrating tablets, comprising the steps of:

(a) spraying onto neutral cores a suspension in a solvent comprising;

(i) oxycodone or a pharmaceutically acceptable salt of oxycodone, and (ii) at least one binding agent, so as to obtain pellets,

(b) applying a subcoat onto said pellets, by spraying thereon a compound soluble in gastric fluid mixed with a solvent, thus obtaining coated pellets,

(c) optionally drying said coated pellets,

(d) applying onto said coated pellets a taste-masking coating comprising a polymer or copolymer with dialkylaminoalkyl(meth)acrylate units and optionally a pore-forming agent, so as to obtain granules,

(e) optionally applying an antistatic coating onto said granules,

(f) mixing acetaminophen, optionally applied onto neutral cores and/or coated, with said granules, at least one disintegrant comprising crospovidone and at least one soluble diluent agent, so as to obtain a powder mixture, and

(g) tableting said powder mixture,

wherein the solvent used in at least one of steps (a) and (b) is a hydroalcoholic solvent.

24. Orally disintegrating tablet obtainable by the process according to claim 23.

25. Orally disintegrating tablet comprising acetaminophen and oxycodone as the only active ingredients, said tablet having an oxycodone content, after dry storage at 80°

C. for 14 days of at least about 90% of the initial oxycodone content before storage.