Pellet formulation for the treatment of the intestinal tract

• US 8,337,886 B2
• Filed: 09/23/2008
• Issued: 12/25/2012
• Est. Priority Date: 07/30/1997
• Status: Expired due to Fees

• Current Assignee: Dr Falk Pharma GmbH
• Original Assignee: Dr Falk Pharma GmbH
• Inventors: Otterbeck, Norbert
• Primary Examiner(s): HUI, SAN MING R
• Application Number:
  US12/236,157
• Publication Number:
  US 20090017117A1
• Time in Patent Office: 1,554 Days
• Field of Search: 424/457, 424/474
• US Class Current: 424/457
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/606 having amino groups
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/141 Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers (co) spray-dried products A61K9/16, (co) lyophilised products A61K9/19; the carrier being chemically bound to the active ingredient A61K47/50
• 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 9/501 Inorganic compounds
• 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 9/5042 Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• 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 35/00 Antineoplastic agents

Abstract

An orally adminsterable pharmaceutical pellet formulation for the treatment of the intestinal tract is disclosed, which comprises a core and an enteric coating, the core including, as a pharmaceutical active compound, aminosalicylic acid or a pharmaceutically tolerable salt or a derivative thereof.

Claims

1. A controlled release pellet formulation for treatment of the intestinal tract, said formulation comprising a core comprising:

1) a homogeneously dispersed pharmaceutically active compound in a non gel-forming polymer matrix and

     2) an enteric coating,

wherein the non gel-forming polymer matrix is essentially insoluble in the intestinal tract and permeable to intestinal fluid made by the process comprising;

mixing the pharmaceutically active compound and the non gel-forming polymer matrix;

scattering in a pharmaceutically tolerable additive; and

extruding a moist mass of the matrix-forming polymer and the active compound.

2. The controlled release pharmaceutical pellet formulation of claim 1, wherein the process further comprises applying an enteric coating to a pellet made from the moist mass.

3. The controlled release pharmaceutical pellet formulation of claim 1, wherein the enteric coating comprises a methacrylic acid containing copolymer or methylhydroxypropyl cellulose phthalate.

4. The controlled release pharmaceutical pellet formulation of claim 3, wherein the methacrylic acid containing copolymer comprises co-poly(methacrylic acid, methyl methacrylate), wherein the co-polymer comprises free carboxylic acid functional groups.

5. The controlled release pharmaceutical pellet formulation of claim 1, wherein the process further comprises cutting the moist mass into pieces.

6. The controlled release pharmaceutical pellet formulation of claim 5, wherein the pieces are about 1 mm long.

7. The controlled release pharmaceutical pellet formulation of claim 5, wherein the process further comprises rounding the pieces in a spheronizer.

8. The controlled release pharmaceutical pellet formulation of claim 7, wherein the process further comprises drying the pieces.

9. The controlled release pharmaceutical pellet formulation of claim 8, wherein the pieces are dried at about 60°

C.

10. The controlled release pharmaceutical pellet formulation of claim 8, wherein the process further comprises:

dissolving poly(methacrylic acid, methylmethacrylate) 1;

1 in an ethanol/water mixture;

suspending triethyl citrate, talc, titanium dioxide and magnesium stearate in the mixture; and

coating the pieces with the suspended mixture.

11. The controlled release pharmaceutical pellet formulation of claim 1, wherein the matrix-forming polymer is selected from the group consisting of poly(ethyl acrylate, methyl methacrylate) and poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride).

12. The controlled release pharmaceutical pellet formulation of claim 1, wherein the non gel-forming polymer matrix makes up at least 1% by weight of the total weight of the core.

13. The controlled release pharmaceutical pellet formulation of claim 1, wherein the pharmaceutically active compound comprises 5-aminosalicylic acid, balsalazide, sulfasalazine or a pharmaceutically acceptable salt thereof.

14. The controlled release pharmaceutical pellet formulation of claim 1, wherein the pharmaceutical pellet formulation is used for the treatment of recurrence of inflammatory intestinal disorders, formation of polyps, intestinal cancer, colorectal polyps or colorectal cancer.

15. The controlled release pharmaceutical pellet formulation of claim 14, wherein the inflammatory intestinal disorders comprise Crohn'"'"'s disease or ulcerative colitis.

16. The controlled release pharmaceutical pellet formulation of claim 1, wherein the pharmaceutical pellet formulation is used for the maintenance of remission of ulcerative colitis.

17. The controlled release pharmaceutical pellet formulation of claim 1, wherein the pellet formulation further comprises pharmaceutically tolerable additives.

18. The controlled release pharmaceutical pellet formulation of claim 1, wherein the pellets of the formulation are about 0.1 mm to about 3 mm in size.

29. A method of maintaining the remission of ulcerative colitis comprising, administering a controlled release pharmaceutical pellet formulation for the treatment of the intestinal tract, which controlled release pharmaceutical pellet formulation is as defined in claim 1.

30. The method of claim 29, wherein the pharmaceutically active compound comprises 5-aminosalicylic acid, balsalazide, sulfasalazine or a pharmaceutically acceptable salt thereof.

31. The method of claim 29, wherein the pharmaceutical pellet formulation is contained in capsules.

32. The method of claim 29, wherein the pharmaceutical pellet formulation is contained in sachets.

33. The method of claim 29, wherein the pharmaceutical pellet formulation is used for the prevention of, treatment of or the prevention of recurrence of inflammatory intestinal disorders, formation of polyps, intestinal cancer, colorectal polyps or colorectal cancer.

34. The method of claim 33, wherein the inflammatory intestinal disorders comprise Crohn'"'"'s disease or ulcerative colitis.

35. The method of claim 29, wherein the pharmaceutical pellet formulation is used for the maintenance of remission of ulcerative colitis.

36. The method of claim 29, wherein the pellet formulation further comprises pharmaceutically tolerable additives.

37. The method of claim 29, wherein the pellets of the formulation are about 0.1 mm to about 3 mm in size.

38. The method of claim 29, wherein the pellet formulation further comprises one or more of microcrystalline cellulose, magnesium stearate, talc, or titanium dioxide.

19. A controlled release pellet formulation for treatment of the intestinal tract, said formulation comprising:

1) a core comprising a homogeneously dispersed pharmaceutically active compound in a non gel-forming polymer matrix and

     2) an enteric coating,

wherein the non gel-forming polymer matrix is essentially insoluble in the intestinal tract and permeable to intestinal fluids, and

wherein the non gel-forming polymer matrix makes up at least 1% by weight of the total weight of the core, and wherein the matrix-forming polymer is selected from the group consisting of poly(ethyl acrylate, methyl methacrylate) and poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride).

20. The controlled release pharmaceutical pellet formulation of claim 19, wherein the pharmaceutically active compound comprises 5-aminosalicylic acid, balsalazide, sulfasalazine or a pharmaceutically acceptable salt thereof.

21. The controlled release pharmaceutical pellet formulation of claim 19, wherein the pharmaceutical pellet formulation is contained in capsules.

22. The controlled release pharmaceutical pellet formulation of claim 19, wherein the pharmaceutical pellet formulation is contained in sachets.

23. The controlled release pharmaceutical pellet formulation of claim 19, wherein the pharmaceutical pellet formulation is used for the treatment of recurrence of inflammatory intestinal disorders, formation of polyps, intestinal cancer, colorectal polyps or colorectal cancer.

24. The controlled release pharmaceutical pellet formulation of claim 23, wherein the inflammatory intestinal disorders comprise Crohn'"'"'s disease or ulcerative colitis.

25. The controlled release pharmaceutical pellet formulation of claim 19, wherein the pharmaceutical pellet formulation is used for the maintenance of remission of ulcerative colitis.

26. The controlled release pharmaceutical pellet formulation of claim 19, wherein the pellet formulation further comprises pharmaceutically tolerable additives.

27. The controlled release pharmaceutical pellet formulation of claim 19, wherein the pellets of the formulation are about 0.1 mm to about 3 mm in size.

28. The controlled release pharmaceutical pellet formulation of claim 19, wherein the pellet formulation further comprises one or more of microcrystalline cellulose, magnesium stearate, talc, or titanium dioxide.