Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery

• US 5,914,132 A
• Filed: 10/11/1996
• Issued: 06/22/1999
• Est. Priority Date: 02/26/1993
• Status: Expired due to Fees

• Current Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Original Assignee: The Procter & Gamble Company
• Inventors: Nakajima, Akio, Kondo, Koji, Kelm, Gary Robert
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Benston, Jr., William E.
• Application Number:
  US08/728,946
• Time in Patent Office: 984 Days
• Field of Search: 424/489, 424/490, 424/497, 424/482
• US Class Current: 424/478
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 47/6951 using cyclodextrin cyclodextrins used as simple excipients A61K47/40
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention relates to a pharmaceutical composition in a unit dosage form for peroral administration in a human or lower animal, having a gastrointestinal tract comprising a small intestine and a colon with a lumen therethrough having an inlet to the colon from the small intestine, comprising:

a. a safe and effective amount of a therapeutically active agent incorporated into a compressed, bi-convex tablet, with a maximum diameter of about 4 mm to about 10 mm;

b. a non-pH dependent smoothing coat applied to the tablet to provide a smooth tablet surface free from edges or sharp curves; and

c. an enteric polymer coating material comprising at least one inner coating layer and only one outer coating layer;

wherein the therapeutically active agent is released at a point near the inlet to, or within the colon; each of the inner coating layer(s) is an enteric polymer that begins to dissolve in an aqueous media at a pH between about 5 to about 6.3; and the outer coating layer is an enteric polymer that begins to dissolve in an aqueous media at a pH between about 6.8 to about 7.2.

Claims

1. A pharmaceutical composition in a unit dosage form for peroral administration in a human or lower animal, having a gastrointestinal tract comprising a small intestine and a colon with a lumen therethrough having an inlet to the colon from the small intestine, comprising:

a. a safe and effective amount of a therapeutically active agent incorporated into a compressed, bi-convex tablet, with a maximum diameter of about 4 mm to about 10 mm;

b. a non-pH dependent smoothing coat applied to the tablet to provide a smooth tablet surface free from edges or sharp curves; and

c. an enteric polymer coating material comprising at least one inner coating layer and only one outer coating layer;

wherein the therapeutically active agent is released at a point near the inlet to, or within the colon;

each of the inner coating layer(s) is an enteric polymer that begins to dissolve in an aqueous media at a pH between about 5 to about 6.3; and

the outer coating layer is an enteric polymer that begins to dissolve in an aqueous media at a pH between about 6.8 to about 7.2.

2. The composition of claim 1 wherein the level of smoothing coat is from about 10% to about 50% of the core tablet weight.

3. The composition of claim 2 wherein the level of smoothing coat is from about 20% to about 40% of the core tablet weight.

4. The composition of claim 2 wherein the non-pH dependent smoothing coat is selected from the group consisting of sucrose, Arabic gum, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol, low viscosity hydroxypropyl cellulose, low viscosity hydroxypropyl methylcellulose, gelatin, sodium alginate, dextrin, psyllium husk powder, and mixtures thereof.

5. The composition of claim 4 wherein the non-pH dependent smoothing coat is selected from the group consisting of sucrose, Arabic gum, low viscosity hydroxypropyl cellulose, low viscosity hydroxypropyl methylcellulose, gelatin, sodium alginate, dextrin, psyllium husk powder, and mixtures thereof.

6. The composition of claim 4 wherein the non-pH dependent smoothing coat additionally comprises a processing agent selected from the group consisting of talc, lactose, precipitated calcium carbonate, titanium dioxide, silica, microcrystalline cellulose and mixtures thereof, to effectively round or smooth out the compressed core tablet.

7. The composition of claim 4 wherein the enteric polymer coating material comprises one inner coating layer.

8. The composition of claim 7 wherein the inner coating layer is selected from the group consisting of cellulose acetate phthalate;

cellulose acetate trimelliate;

hydroxypropyl methylcellulose phthalate;

hydroxypropyl methylcellulose acetate succinate;

polyvinyl acetate phthalate;

poly(methacrylic acid, methyl methacrylate) 1;

1;

poly(methacrylic acid, ethyl acrylate) 1;

1; and

compatible mixtures thereof.

9. The composition of claim 8 wherein the inner coating layer is selected from the group consisting of poly(methacrylic acid, methyl methacrylate) 1:

1;

poly(methacrylic acid, ethyl acrylate) 1;

1; and

compatible mixtures thereof.

10. The composition of claim 9 wherein the inner coating layer is poly( methacrylic acid, ethyl acrylate) 1:

1, which has a coating thickness of about 120 μ

m to about 350 μ

m when the diameter is about 4 mm.

11. The composition of claim 9 wherein the inner coating layer is poly(methacrylic acid, ethyl acrylate) 1:

1, which has a coating thickness of about 100 μ

m to about 300 μ

m when the diameter is about 7 mm.

12. The composition of claim 9 wherein the inner coating layer is poly(methacrylic acid, methyl methacrylate) 1:

1, which has a coating thickness of about 110 μ

m to about 300 μ

m when the diameter is about 4 mm.

14. The composition of claim 7 wherein the outer coating layer is selected from the group consisting of poly(methacrylic acid, methyl methacrylate) 1:

2, and a mixture of poly(methacrylic acid, methyl methacrylate) 1;

1 and poly(methactylic acid, methyl methacrylate) 1;

2 in a ratio of about 1;

10 to about 1;

2.

15. The composition of claim 14 wherein the outer coating layer is poly(methacrylic acid, methyl methacrylate) 1:

2.

16. The composition of claim 1 wherein the therapeutically active agent is selected from the group consisting of picosulfate, sennosides, anti-diarrheals, nonsteroidal anti-inflammatory agents, glucocorticoids, antimicrobials, immunosuppressants, chemotherapeutics, peptides, proteins, beta blockers, calcium channel blockers, ACE inhibitors, H2-blockers, antiasthmatic agents, and antihistamines.

17. A method for providing delivery of a therapeutically active agent to the colon of a human or lower animal by administering a safe and effective amount of the composition of claim 1 perorally.

13. The composition ofeclaim 9 wherein the inner coating, layer is poly(methacrylic acid, methyl methacrylate) 1:

1, which has a coating, thickness of about 90 μ

m to about 250 μ

m when the diameter is about 7 mm.