Pellet formulation for the treatment of the intestinal tract

• US 6,551,620 B2
• Filed: 07/16/2001
• Issued: 04/22/2003
• Est. Priority Date: 07/30/1997
• Status: Expired due to Term

• Current Assignee: Dr Falk Pharma GmbH
• Original Assignee: Dr Falk Pharma GmbH
• Inventors: Otterbeck, Norbert
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Pulliam, Amy E
• Application Number:
  US09/906,494
• Publication Number:
  US 20010055616A1
• Time in Patent Office: 645 Days
• Field of Search: 424/464, 424/465, 424/468, 424/469, 424/486, 424/487, 424/489, 424/490, 514/159, 514/166
• US Class Current: 424/489
• 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. An orally administrable pharmaceutical pellet formulation having a controlled release profile for the treatment of the intestinal tract, which comprises a core and an enteric coating and optionally pharmaceutically tolerable additives, the core including, as a pharmaceutical active compound, aminosalicylic acid or a pharmaceutically acceptable salt, wherein the active compound is present in the core in a non gel-forming polymer matrix which is essentially insoluble in the intestinal tract and permeable to intestinal fluids and the active compound, the matrix-forming polymer making 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).

2. The pellet formulation as claimed in claim 1, wherein the matrix-forming polymer makes up 4-10% by weight of the total weight of the core.

3. The pellet formulation as claimed in claim 1 wherein the polymer matrix extends through the entire core and the active compound is homogeneously dispersed in the polymer matrix.

4. The pellet formulation as claimed in claim 1, wherein the active compound is 5-aminosalicylic acid.

5. The pellet formulation as claimed in claim 1, wherein the enteric coating comprises a methacrylic acid copolymer or methylhydroxypropyl-cellulose phthalate.

6. The pellet formulation as claimed in claim 5, wherein the enteric coating contains poly(methacrylic acid, methyl methacrylate), the polymer containing free carboxyl groups as functional groups.

7. The pellet formulation as claimed in claim 1, wherein the pellet only comprises one coating layer.

8. The pellet formulation as claimed in claim 1, comprising, as an active compound, 5-aminosalicylic acid in a poly(ethyl acrylate, methyl methacrylate) 2:

1 matrix, the polymer containing ester groups as functional groups, in the core and an enteric coating which comprises poly(methacrylic acid, methyl methacrylates) 1;

1 or 1;

2, the polymer containing free carboxyl groups as functional groups, and optionally pharmaceutically tolerable additives.

9. The pellet formulation as claimed in claim 1, wherein the release of active compound in 0.1 M HCl after 2 hours is less than 10%, and in artificial gastric juice at pH of about 6.8 after 30 minutes is 10-30%, after 2 hours is 40-60%, and after 6 hours is at least 80%.

10. A pharmaceutical formulation, which comprises pellets as claimed in claim 1.

11. The pharmaceutical formulation as claimed in claim 10, which is a gelatin capsule or a tablet which contains the pellets.

12. A method for treating, or preventing the recurrence of intestinal disorders, secondary disorders resulting therefrom, or intestinal cancer comprising administering the pellet formulation of claim 1 to a patient in need thereof.

13. The method of claim 12, wherein the intestinal disorder is an inflammatory intestinal disorder in the active or remission phase.

14. The method of claim 12, wherein the intestinal disorder is a polyp in the gastrointestinal tract.

15. The method of claim 14, wherein the polyp is an adenoma or shows polypous growth.

16. The method of claim 14, wherein the pellet formulation lowers the recurrence rate of adenomas or colorectal polyps compared to a method free of administering the formulation.

17. A method for treating colon cancer comprising administering the pellet formulation of claim 1 to a patient in need thereof.