|Title:||Delayed release tablet with defined core geometry|
|Abstract:|| A tablet comprising a core containing an active agent, and a coating, the core being disposed within the coating such that the coating has a thickness about a longitudinal axis (X-Y) of about 4.85 to 4.95 mm. The position of the core within the coating dictating that the active agent is released rapidly after a lag time during which time no active agent is released.|
|Inventor(s):|| Vergnault; Guy (Kembs, FR), Grenier; Pascal (Kappelen, FR), Dragan; Christophe (Geispitzen, FR) |
|Assignee:|| Jagotec AG (Muttenz, CH) |
1. A press-coated tablet comprising a defined core containing a pharmaceutically active agent, and a compression coating around said core, the core being disposed within
said compression coating such that the coating thickness about an axis (X-Y) is thicker and less dense than the coating about an axis (A-B) orthogonal to (X-Y), wherein said compression coating is formed of an insoluble or poorly water soluble
hydrophobic material and said coating is sufficiently porous about the (X-Y) plane of the tablet to permit the ingress of aqueous media to the core at a rate to ensure release of the active agent after a period of time between 2 to 6 hours wherein said
period of time is followed by rupture of the coating along the X-Y axis, wherein the compression coating lacks ingredients that swell and gel to such an extent that the coating acts as a diffusion barrier to the release of the active agent.
2. The tablet of claim 1, wherein the coating thickness about the axis (X-Y) is about 2.2 mm to about 2.6 mm and the thickness about the orthogonal axis (A-B) is about 1.0 to about 1.6 mm.
3. The tablet of claim 1, wherein said water insoluble or poorly soluble hydrophobic material is selected from the group consisting of hydrophobic cellulosic derivatives and polymers including alkylcellulose, hydroxypropyl cellulose,
hydroxypropylmethyl cellulose, carboxymethyl cellulose, and derivatives thereof; polymethacrylic polymers, polyvinyl acetate and cellulose acetate polymers, fatty acids, fatty acid esters, fatty acid salts, long chain fatty alcohols, polyoxyethylene
alkyl ethers, polyoxyethylene stearates, sugar esters, lauroyl macrogol-32 glyceryl, and stearoyl macrogol-32 glyceryl, and combinations thereof.
4. The tablet of claim 1, wherein the coating comprises calcium phosphate salt, glyceryl behenate, and polyvinyl pyrollidone, or mixtures thereof.
5. The tablet of claim 1, wherein the core comprises a disintegrating agent.
6. The tablet of claim 1, further comprising cross-linked polyvinyl pyrollidone and croscarmellose sodium.
7. The tablet of claim 1, wherein the active agent is a glucocorticosteroid selected from prednisone, prednisolone or methylprednisolone.
8. The tablet of claim 7, wherein the active agent is prednisone and the prednisone is present in an amount of 1 mg or 5 mg.
9. The tablet of claim 8, wherein the prednisone is present in an amount of 5 mg and the tablet comprises the following ingredients in each of the core and coating in a weight percentage by weight of each of the core and coating: Core:
Prednisone 8.33% Lactose monohydrate 64.47% Povidone 6.67% Croscarmellose sodium 18.33% Coating Dibasic calcium phosphate dihydrate 50% Glyceryl behenate 40% Povidone 8.40%.
10. The tablet of claim 1, wherein the active agent is a sympathomimetic agent.
11. The tablet of claim 10, wherein the active agent is terbutaline sulphate.
12. The tablet of claim 10, wherein the active agent is present in amounts of 1 to 50% based on the weight of the core.
13. The tablet of claim 1, wherein the tablet has 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 of purified water such that there is a median lag time
of about 4 hours and at least 80% of active agent is released after 4.5 hours and about 100% of the active agent is released after 5 hours.
14. The tablet of claim 13, wherein the active agent is selected from prednisone, prednisolone or methylprednisolone.
15. The tablet of claim 1, wherein the ratio of coating thickness about the X:Y to A:B axes is 1.3-2.6 to 1.
16. The tablet of claim 1, wherein at least 80% of the active agent is released after 4.5 hours.
17. The tablet of claim 1, wherein about 100% of the active agent is released after 5 hours.
18. A method of administering a glucocorticosteroid active substance selected from prednisone, prednisolone or methylprednisolone to a patient in need thereof, the method comprising administering the tablet of claim 7 to the subject.
19. A method of making the tablet of claim 1, the method comprising the steps of forming a first granulate containing coating material; providing a second granulate containing core material; forming the second granulate into a core; and
press coating the first granulate around the core.