Controlled release dosage forms

• US 20040037883A1
• Filed: 02/21/2003
• Published: 02/26/2004
• Est. Priority Date: 02/21/2002
• Status: Active Grant

• Current Assignee: Bausch Health Ireland Limited (Bausch Health Cos., Inc.)
• Original Assignee: Biovail Laboratories International Srl (Bausch Health Cos., Inc.)
• Inventors: Zhou, Fang, Maes, Paul
• Granted Patent: US 7,780,987 B2
• Time in Patent Office: Days
• US Class Current: 424/471
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• 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 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2853 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The invention provides stable controlled release monolithic coating compositions for use in coating pharmaceutical oral dosage forms comprising a polyglycol having a melting point greater than 55° C. and an aqueous dispersion of a neutral ester copolymer lacking functional groups.

Claims

1. A stable controlled release monolithic coating composition for use in coating a pharmaceutical oral dosage form, said coating comprising:

a) an aqueous dispersion of a neutral ester copolymer without any functional groups;

b) a poly glycol having a melting point greater than 55°

C., and

c) one or more pharmaceutically acceptable excipients;

wherein said coating composition is coated onto said pharmaceutical oral dosage form and cured at a temperature at least equal to or greater than the melting point of said poly glycol.

2. The stable controlled release coating composition of claim 1 wherein said neutral ester copolymer without any functional groups is selected from the group consisting of Eudragit NE30D, Eudragit NE40D and any combination thereof.

3. The stable controlled release coating composition of claim 2 wherein said neutral ester copolymer without any functional groups is NE30D.

4. The stable controlled release coating composition of claim of claim 1 wherein said neutral ester copolymer without any functional groups is present in an amount of from about 1% to about 35% by weight of the coating composition.

5. The stable controlled release coating composition of claim 4 wherein said neutral ester copolymer without any functional groups is present in an amount of from about 1% to about 25% by weight of the coating composition.

6. The stable controlled release coating composition of claim 5 wherein said neutral ester copolymer without any functional groups is present in an amount of from about 1% to about 7%.

7. The stable controlled release coating composition of claim 1 wherein said poly glycol is selected from the group consisting of polyethylene glycol 8000, polyethylene glycol 10000, polyethylene glycol 20000, Poloxamer 188, Poloxamer 338, Poloxamer 407, Polyethylene Oxides, Polyoxyethylene Alkyl Ethers, Polyoxyethylene Sorbitan Fatty Acid Esters, and Polyoxyethylene Stearates.

8. The stable controlled release coating composition of claim 1 wherein said poly glycol is selected from the group consisting of polyethylene glycol 8000, polyethylene glycol 10000, polyethylene glycol 20000 and any combination thereof.

9. The stable controlled release coating composition of claim 8 wherein said polyethylene glycol is polyethylene glycol 8000.

10. The stable controlled release coating composition of claim 1 wherein said polyethylene glycol or derivative thereof is present in an amount of from about 0.1% to about 10% by weight of the coat composition.

14. The stable controlled release coating composition of claim 1 wherein the one or more pharmaceutically acceptable excipients is selected from the group consisting of anti-tacking agents, emulsifying agents, hydrophilic agents, anti-foaming agents, flavourants, colourants, sweeteners and any combination thereof.

15. The stable controlled release coating composition of claim 14 wherein the anti-tacking agent is selected from the group consisting of adipic acid, magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, glyceryl monostearate, talc, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate and any combination thereof.

16. The stable controlled release coating composition of claim 15 wherein the anti-tacking agent is talc.

17. The stable controlled release coating composition of claim 15 wherein the anti-tacking agent is present in an amount of from about 1% to about 15% by weight of the coating composition.

18. The stable controlled release coating composition of claim 16 wherein the anti-tacking agent is present in an amount of from about 1% to about 7%.

19. The stable controlled release coating composition of claim 14 wherein said hydrophilic agent is selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose and any combination thereof.

20. The stable controlled release coating composition of claim 19 wherein said hydrophilic agent is hydroxypropyl methylcellulose.

21. The stable controlled release coating composition of claim 19 wherein said hydrophilic agent is present in an amount from about 0.1% to about 10% by weight of the coat composition.

22. The stable controlled release coating composition of claim 21 wherein said hydrophilic agent is present in an amount from about 0.1% to about 6% by weight of the coat composition.

23. The stable controlled release coating composition of claim 22 wherein said hydrophilic agent is present in an amount from about 0.1% to about 3% by weight of the coating composition.

24. The stable controlled release coating composition of claim 14 wherein said anti-foaming agent is selected from the group consisting of silicon oil, simethicone and any combination thereof.

25. The stable controlled release coating composition of claim 24 wherein said anti-foaming agent is simethicone.

26. The stable controlled release coating composition of claim 24 wherein said anti-foaming agent is present in an amount up to about 0.5% by weight of the coating composition.

27. The stable controlled release coating composition of claim 26 wherein said anti-foaming agent is present in an amount from about 0.1% to about 0.4% by weight of the coating composition.

28. The stable controlled release coating composition of claim 14 wherein said emulsifying agent is selected from the group consisting of polysaccharides, glycerol esters, cellulose ethers, sorbitan esters, polysorbates and any combination thereof.

29. The stable controlled release coating composition of claim 28 wherein said polysorbate is polyoxyethylene sorbitan mono-oleate.

30. The stable controlled release coating composition of claim 29 wherein said polyoxyethylene sorbitan mono-oleate is present in an amount of up to about 0.5% by weight of the coat composition.

31. The stable controlled release coating composition of claim 30 wherein said polyoxyethylene sorbitan mono-oleate is present in an amount of from about 0.1% to about 0.3% by weight of the coat composition.

32. The stable controlled release coating composition of claim 14 wherein said colorant is selected from group consisting of iron oxide pigments, titanium dioxide, aluminum Lakes and any combination thereof.

33. The stable controlled release coating composition of claim 32 wherein said colorant is titanium dioxide.

34. The stable controlled release coating composition of claim 32 wherein said colorant is present in an amount of from about 0.1% to about 10% by weight of the coat composition.

35. The stable controlled release coating composition of claim 34 wherein said colorant is present in an amount of from about 0.1% to about 5% by weight of the coat composition.

36. The stable controlled release coating composition of claim 35 wherein said colorant is present in an amount of from about 0.1% to about 2% by weight of the coat composition.

37. The stable controlled release coating composition of claim 1 wherein said pharmaceutical oral dosage form is selected from the group consisting of tablets and capsules.

11. The stable controlled release coating composition of 10 wherein said polyethylene glycol or derivative there of is present in an amount of from about 0.1% to about 5% by weight of the coat composition.

12. The controlled release coating composition of claim 11 wherein said polyethylene glycol or derivative thereof is present in an amount of from about 0.1% to about 3% by weight of the coat composition.

13. The controlled release coating composition of claim 12 wherein said polyethylene glycol or derivative thereof is present in an amount of from about 0.1% to about 0.5% by weight of the coat composition.

38. A stable controlled release monolithic coating composition for use in coating a pharmaceutical oral dosage form, said coating comprising an aqueous dispersion of Eudragit NE30D, polyethylene glycol 8000, hydroxypropyl methylcellulose, talc, simethicone, titanium dioxide, and polyoxyethylene sorbitan mono-oleate, said Eudragit NE30D is present in an amount of from about 1% to about 35% by weight of the coat composition, said polyethylene glycol is present in an amount of from about 0.1% to about 3% by weight of the coat composition, said hydroxypropyl methylcellulose is present in an amount of from about 0.1% to about 6% by weight of the coat composition , said talc is present in an amount of from about 0. 1% to about 7% by weight of the coat composition, said simethicone is present in an amount up to about 0.5% by weight of the coat composition, said polyoxyethylene sorbitan mono-oleate is present in an amount of up to about 0.5% by weight of the coat composition, said titanium dioxide is present in an amount of from about 0.% to about 2% by weight of the coat composition;

and composition is coated onto said pharmaceutical oral dosage form and cured at a temperature at least equal to or greater than the melting point of said polyglycol.

39. The controlled release oral dosage form of claim 38, wherein said pharmaceutical dosage form is selected from the group consisting of tablets and capsules.

40. A controlled release oral dosage form comprising:

a) a core, wherein said core comprises;

i) an effective amount of at least one therapeutically active agent, and

ii) one or more first pharmaceutically acceptable excipients, and

b) a stable controlled release monolithic coating composition for coating said core, said coating composition comprising;

i) an aqueous dispersion of a neutral ester copolymer without any functional groups;

ii) a poly glycol having a melting point greater than 55°

C., and

iii) one or more second pharmaceutically acceptable excipients;

wherein said coating composition is coated onto said core and cured at a temperature at least equal to or greater than the melting point of the poly glycol.