Delayed release tablet with defined core geometry

• US 8,168,218 B2
• Filed: 04/23/2004
• Issued: 05/01/2012
• Est. Priority Date: 04/24/2003
• Status: Active Grant

• Current Assignee: Jagotec Ag (Vectura Group Ltd.)
• Original Assignee: Jagotec Ag (Vectura Group Ltd.)
• Inventors: Vergnault, Guy, Grenier, Pascal, Dragan, Christophe
• Primary Examiner(s): Dickinson, Paul
• Application Number:
  US10/554,538
• Publication Number:
  US 20070110807A1
• Time in Patent Office: 2,930 Days
• Field of Search: None
• US Class Current: 424/464
• CPC Class Codes: A61J 1/03 for pills or tablets containers for pills or tablets with special dispensing means therefor B65D83/04
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• 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 9/2813 Inorganic compounds
• CPC Class Codes: A61K 9/282 Organic compounds, e.g. fats
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• 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 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14

Abstract

A press-coated tablet comprising a core containing an drug substance, and a coating, the core being disposed within the coating such that the coating has a first thickness about an axis A-B and a thickness about an orthogonal axis X-Y, such that the coating about the axis X-Y is thicker than the coating about the axis A-B, and is adapted to provide a lag time of between about 2 to 6 hours during which substantially no drug substance is released.

Claims

1. A press-coated tablet comprising a core containing 5 mg of prednisone and a coating around the core, said core being disposed within said coating such that the coating thickness about an axis (X-Y) is thicker than the coating about an axis (A-B) orthogonal to (X-Y),

wherein the thickness of the coating about the axis (X-Y) is selected such that the coating ruptures upon immersion in an aqueous medium after a period of between about 2 to about 6 hours to release the drug,

wherein coating material about the (X-Y) axis is relatively less dense than the coating material disposed about the (A-B) axis and the coating material about the (X-Y) axis is more permissive towards ingress of aqueous media than the coating material disposed about the axis (A-B),

and wherein the axis (A-B) is the axis of the direction of movement of the punch used in the press-coating of the tablet:

said tablet comprising the following ingredients

Core of 5 mg prednisone tablet;

Prednisone 8.33% as a percentage by weight in said core;

Lactose monohydrate 64.47% as a percentage by weight in said core;

Povidone 6.67% as a percentage by weight in said core;

Croscarmellose sodium 18.33% as a percentage by weight in said core;

Red ferric oxide 0.5% as a percentage by weight in said core;

Magnesium stearate Vegetable origin 1.0% as a percentage by weight in said core;

Colloidal silicon dioxide 0.5% as a percentage by weight in said core;

Coating;

Dibasic calcium phosphate dihydrate 50% as a percentage by weight in said coating;

Glyceryl behenate 40% as a percentage by weight in said coating;

Povidone 8.40% as a percentage by weight in said coating;

Yellow ferric oxide 0.1% as a percentage by weight in said coating;

Magnesium stearate Vegetable origin 1.0% as a percentage by weight in said coating;

Colloidal silicon dioxide 0.5% as a percentage by weight in said coating.

2. The tablet according to claim 1 wherein, upon administration to a patient, the lag time before drug release is 2 to 6 hours.

3. The tablet according to claim 1, said tablet having an in vitro dissolution profile using USP dissolution apparatus No. 2, at a stirring rate of 100 rpm and in a dissolution medium of 500 mL purified water, wherein said dissolution profile comprises a median lag time of about 4 hours with at least 80% of a drug substance being released after 4.5 hours and about 100% of the drug substance being released after 5 hours.

4. The tablet according to claim 1 wherein intra-subject or inter-subject variability in T_max differs by less than +/−

20% whether or not a patient is in a fed or a fasted (fed/fasted) state.

5. The tablet according to claim 1 wherein upon administration to a patient the ratio of C_max fed/fasted upon single dosing is 0.7 to 1.43.

6. The tablet according claim 1 wherein upon administration to a patient the ratio of AUC fed/fasted upon single dosing is 0.8 to 1.25.

7. A pharmaceutical package containing a tablet according to claim 1 together with labelling or instructions that the tablet can be taken with or without food.

8. A method of treating arthritic pain, allergies, asthma, Crohn'"'"'s disease, ulcerative colitis, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) by providing to a patient in need of treatment a tablet according to claim 1.

9. A method of preparing a tablet according to claim 1 comprising the steps of:

(a) forming a first granulate-containing coating material;

(b) forming a core comprising a second granulate-containing core material; and

(c) press coating the first granulate-containing coating material around the core.