ENTERIC COATED PARTICLES CONTAINING AN ACTIVE INGREDIENT

• US 20070292510A1
• Filed: 06/18/2007
• Published: 12/20/2007
• Est. Priority Date: 06/19/2006
• Status: Abandoned Application

• Current Assignee: McNeil-PPC Incorporated (Johnson & Johnson)
• Original Assignee: McNeil-PPC Incorporated (Johnson & Johnson)
• Inventors: Huang, Hugh
• Application Number:
  US11/764,287
• Publication Number:
  US 20070292510A1
• Time in Patent Office: Days
• US Class Current: 424/470
• 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 9/2081 with microcapsules or coated microparticles according to A61K9/50
• 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 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings

Abstract

Enterically coated particles and chewable tablets made therefrom are disclosed. The enterically coated particles are comprised of a core containing an active ingredient, a first coating layer comprised of polymeric composition having a Tg less than about 40° C. that substantially covers the core; and a second coating layer, which substantially covers the first coating layer, comprised of a high temperature film forming polymer. The particles may be produced into a tablet form, such as a chewable tablet form, that provides for the immediate release of the active ingredient.

Claims

1. An enterically coated particle comprising

a) a particle core containing an active ingredient;

b) a first layer that substantially covers the core and has a surface; and

c) a second layer on the surface of the first layer,

wherein the first layer has a Tg less than about 40°

C. and the second layer has a Tg greater than about 56°

C.

2. The particle of claim 1, wherein the second layer substantially covers the first layer.

3. The particle of claim 1, wherein the first layer is present in an amount, based upon the total weight of the coated particle, from about 5% to about 50% and the second layer is present in an amount, based upon the total weight of the coated particle, from about 3% to about 20%.

4. The particle of claim 1, wherein the active ingredient is selected from the group consisting of a nonsteroidal anti-inflammatory drug, aspirin, acetaminophen, pseudoephedrine, phenylpropanolamine, chlorpheniramine, dextromethorphan, diphenhydramine, dimenhydrinate, meclizine, famotidine, loperamide, ranitidine, cimetidine, astemizole, loratadine, desloratadine, fexofenadine, cetirizine, antacids, modafinil, methylphenidate, oxybutynin, pharmaceutically acceptable salts thereof, metabolites thereof, and mixtures thereof.

5. The particle of claim 1, wherein the first layer is comprised of methacrylic acid-methacrylic acid ester copolymers;

cellulose acetate phthalate;

polyvinyl acetate phthalate;

shellac;

hypromellose phthalate;

or derivatives, copolymers or mixtures thereof.

6. The particle of claim 5, wherein the first layer is comprised of a methacrylic acid-methylacrylic acid ester copolymer having a mean molecular weight of about 800,000.

7. The particle of claim 1, wherein the first layer is comprised of, based upon the total dry weight of the first layer:

a) from about 60 percent to about 80 percent of a film forming material having a Tg greater than about 70°

C.; and

b) from about 20 percent to about 40 percent of a plasticizer.

8. The particle of claim 1, wherein the first layer is comprised of, based upon the total dry weight of the first layer:

a) from about 60 percent to about 80 percent of methacrylic acid-methyl methacrylate copolymer having a Tg greater than about 70°

C.; and

b) from about 20 percent to about 40 percent of a plasticizer.

9. The particle of claim 1 wherein the second layer is comprised of, based upon the total dry weight of the second layer:

a) from about 80 percent to about 95 percent of a film forming material having a Tg greater than about 70°

C.; and

b) from about 5 percent to about 20 percent of a plasticizer.

10. The particle of claim 1, wherein the first layer is comprised of, based upon the total dry weight of the first layer:

a) from about 60 percent to about 80 percent of a film forming material selected from the group consisting of methyacrylic acid-methyacrylic acid ester copolymer, cellulose acetate phthalate, polyvinylacetate phthalate, shellac, hypromellose phthalate, and derivatives, copolymers and mixtures thereof; and

b) from about 20 percent to about 40 percent of a plasticizer.

11. The particle of claim 8, wherein the plasticizer is selected from the group consisting of polyethylene glycol;

propylene glycol;

glycerin;

triethyl citrate;

tributyl citrate;

dibutyl sebecate;

vegetable oils;

surfactants;

mono acetate of glycerol;

diacetate of glycerol;

triacetate of glycerol;

triacetin;

acetyltributyl citrate;

dibutylsuccinate;

hydrogenated castor oil;

fatty acids;

substituted triglycerides; and

glycerides; and

mixtures thereof.

12. The particle of claim 9, wherein the plasticizer is selected from the group consisting of polyethylene glycol;

propylene glycol;

glycerin;

triethyl citrate;

tributyl citrate;

dibutyl sebecate;

vegetable oils;

surfactants;

mono acetate of glycerol;

diacetate of glycerol;

triacetate of glycerol;

triacetin;

acetyltributyl citrate;

dibutylsuccinate;

hydrogenated castor oil;

fatty acids;

substituted triglycerides; and

glycerides; and

mixtures thereof.

13. The particle of claim 1, wherein the first layer possesses an elongation at break value of at least about 70%.

14. The particle of claim 1, wherein the second layer is comprised of copolymers of acrylic acid esters.

15. The particle of claim 1, wherein the second layer is comprised of a film forming copolymer comprising a reaction product of polymethacrylic acid and at least one member of the group consisting of acrylic acid ester and polymethacrylic acid ester.

16. The particle of claim 1 wherein the first layer comprises, based upon the total weight of the first layer, at least about 50 percent of an enteric polymer.

17. A tablet comprised of the particles of claim 1.

18. A chewable tablet comprised of the particles of claim 1.

19. The chewable tablet of claim 18, wherein the active ingredient is a nonsteroidal anti-inflammatory drug, aspirin, acetaminophen, pseudoephedrine, phenylephrine, phenylpropanolamine, chlorpheniramine, dextromethorphan, diphenhydramine, dimenhydrinate, meclizine, chophedianol, famotidine, loperamide, ranitidine, cimetidine, astemizole, loratadine, modafinil, methylphenidate, oxybutynin, desloratadine, fexofenadine, cetirizine, antacids, or pharmaceutically acceptable salts, metabolites, or mixtures thereof.

20. A chewable tablet comprised of enterically coated particles, said particles comprising

a) a particle core containing an active ingredient;

b) a first layer that substantially covers the core, said first layer having a surface; and

c) a second layer that substantially covers the surface of the first layer,

wherein the first layer has a Tg less than about 40°

C. and the second layer has a Tg greater than about 56°

C., and the first layer is comprised of methacrylic acid-methacrylic acid ester copolymers;

cellulose acetate phthalate;

polyvinyl acetate phthalate;

shellac;

hypromellose phthalate;

or derivatives, copolymers, or mixtures thereof.

21. The chewable tablet of claim 20, wherein the first layer is comprised of a methacrylic acid-methyacrylic acid ester copolymer having a mean molecular weight of about 800,000.

22. The chewable tablet of claim 20, wherein the first layer is comprised of, based upon the total dry weight of the first layer:

a) from about 60 percent to about 80 percent of a film forming material having a Tg greater than about 70°

C.; and

b) from about 20 percent to about 40 percent of a plasticizer.

23. The chewable tablet of claim 20, wherein the first layer is comprised of, based upon the total dry weight of the first layer:

a) from about 60 percent to about 80 percent of methacrylic acid-methacrylic acid ester copolymer; and

b) from about 20 percent to about 40 percent of a plasticizer.

24. The chewable tablet of claim 20, wherein the first layer is comprised of, based upon the total dry weight of the first layer:

a) from about 60 percent to about 80 percent of a film forming material selected from the group consisting of methacrylic acid-methacrylic acid ester copolymer, cellulose acetate phthalate, polyvinylacetate phthalate, shellac, hypromellose phthalate, and derivatives, copolymers, and mixtures thereof; and

from about 20 percent to about 40 percent of a plasticizer.

25. The chewable tablet of claim 22, wherein the plasticizer is selected from the group consisting of polyethylene glycol;

propylene glycol;

glycerin;

sorbitol;

triethyl citrate;

tributyl citrate;

dibutyl sebecate;

vegetable oils;

surfactants;

mono acetate of glycerol;

diacetate of glycerol;

triacetate of glycerol;

natural gums;

triacetin;

acetyltributyl citrate;

diethyloxalate;

diethylmalate;

diethyl fumarate;

diethylmalonate;

dioctylphthalate;

dibutylsuccinate;

glyceroltributyrate;

hydrogenated castor oil;

fatty acids;

substituted triglycerides and glycerides; and

mixtures thereof.

26. The chewable tablet of claim 23, wherein the plasticizer is selected from the group consisting of polyethylene glycol;

propylene glycol;

glycerin;

sorbitol;

triethyl citrate;

tributyl citrate;

dibutyl sebecate;

vegetable oils;

surfactants;

mono acetate of glycerol;

diacetate of glycerol;

triacetate of glycerol;

natural gums;

triacetin;

acetyltributyl citrate;

diethyloxalate;

diethylmalate;

diethyl fumarate;

diethylmalonate;

dioctylphthalate;

dibutylsuccinate;

glyceroltributyrate;

hydrogenated castor oil;

fatty acids;

substituted triglycerides and glycerides; and

mixtures thereof.

27. The chewable tablet of claim 20, wherein the first layer possesses an elongation at break value of at least about 70%.

28. The chewable tablet of claim 20, wherein the second layer is comprised of copolymers of acrylic acid esters.

29. The chewable tablet of claim 20, wherein the second layer is comprised of a film forming copolymer comprising a reaction product of polymethacrylic acid and at least one member of the group consisting of acrylic acid ester and polymethacrylic acid ester.

30. The chewable tablet of claim 20, wherein the first layer comprises, based upon the total weight of the first layer, at least about 20 percent of an enteric polymer.

31. A chewable tablet comprised of at least one first particle and at least one second particle, said first particle is comprised of

a) a first particle core containing a first active ingredient;

b) a first layer that substantially covers the first particle core, the first layer having a surface; and

c) a second layer on the surface of the first layer, the second coating layer having a Tg greater than about 56°

C.,

wherein the first layer has a Tg less than about 40°

C. and is comprised of methacrylic acid-methacrylic acid ester copolymers;

cellulose acetate phthalate;

polyvinyl acetate phthalate;

shellac;

hypromellose phthalate;

or derivative, copolymers, or mixtures thereof; and

said second particle comprising a second particle core containing a second active ingredient.

32. The chewable tablet of claim 31, wherein the second layer is comprised of copolymers of acrylic acid esters.

33. The chewable tablet of claim 31, wherein the second layer is comprised of a film forming copolymer comprising a reaction product of polymethacrylic acid and at least one member of the group consisting of acrylic acid ester and polymethacrylic acid ester.

34. A meltaway dosage form comprised of enterically coated particles, said particles comprising

a) a particle core containing an active ingredient;

b) a first layer that substantially covers the core, said first layer having a surface; and

d) a second layer that substantially covers the surface of the first layer,

wherein the first layer has a Tg less than about 40°

C. and the second layer has a Tg greater than about 56°

C., and the first layer is comprised of methacrylic acid-methacrylic acid ester copolymers;

cellulose acetate phthalate;

polyvinyl acetate phthalate;

shellac;

hypromellose phthalate;

or derivatives, copolymers, or mixtures thereof.