Delayed release tablet with defined core geometry

• US 20070110807A1
• Filed: 04/23/2004
• Published: 05/17/2007
• 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
• Granted Patent: US 8,168,218 B2
• Time in Patent Office: Days
• US Class Current: 424/472
• 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 tablet comprising a core containing a drug, 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 6 hours to release the drug.

2. The tablet according to claim 1 wherein the coating thickness about the axis (X-Y) is at least 2.2 mm.

3. The tablet according to claim 1 wherein the coating thickness about the axis (X-Y) is about 2.2 mm to about 2.6 mm.

4. The tablet according to claim 1 wherein the coating is a water insoluble or poorly soluble hydrophobic material.

5. The tablet according to claim 1 wherein the coating contains hydrophobic cellulosic derivatives and polymers selected from alkylcellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose and derivatives thereof;

polymethacrylic polymers, polyvinyl acetate polymers, cellulose acetate polymers;

fatty acid esters, fatty acid salts;

long chain fatty alcohols;

polyoxyethylene alkyl ethers;

polyoxyethylene stearates;

sugar esters;

lauroyl macrogol-32 glyceryl, stearoyl macrogol-32 glyceryl and combinations thereof.

6. The tablet according to claim 1 wherein the coating comprises calcium phosphate salt, glyceryl behenate, polyvinyl pyrollidone, or mixtures thereof.

7. The tablet according to claim 1 wherein the core comprises a drug substance and a disintegrating agent.

8. The tablet according to claim 1 containing cross-linked polyvinyl pyrollidone and croscarmellose sodium.

9. The tablet according to claim 1 wherein the active substance is a glucocorticosteroid selected from prednisone, prednisolone, or methylprednisolone.

10. The tablet according to claim 9 comprising 1 mg prednisone.

11. The tablet according to claim 21 containing the following ingredients:

Core of 5 mg prednisone tablet;

Prednisone 8.33%;

Lactose monohydrate 64.47%;

Povidone 6.67%;

Croscarmellose sodium 18.33%;

Red ferric oxide 0.5%;

Magnesium stearate Vegetable origin 1.0%;

Colloidal silicon dioxide 0.5%;

Coating;

Dibasic calcium phosphate dihydrate 50%;

Glyceryl behenate 40%;

Povidone 8.40%;

Yellow ferric oxide 0.1%;

Magnesium stearate Vegetable origin 1.0%;

Colloidal silicon dioxide 0.5%;

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

13. 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 purified water (500 ml), wherein said dissolution profile comprises a median lag time of about 4 hours with at least about 80% of a drug substance being released after 4.5 hours and about 100% of the drug substance being released after 5 hours.

14. The tablet according to claim 13 wherein the drug substance is selected from prednisone, prednisolone or methylprednisolone.

15. 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.

16. 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.

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

18. 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.

19. 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 containing prednisone, prednisolone, or methylprednisolone.

20. 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.

21. The tablet according to claim 9 comprising 5 mg prednisone.