Triple Combination Release Multi-Layered Tablet

• US 20080299197A1
• Filed: 06/18/2008
• Published: 12/04/2008
• Est. Priority Date: 12/29/2005
• Status: Active Grant

• Current Assignee: Acella Holdings LLC
• Original Assignee: Osmotica Corp.
• Inventors: Meyer, Glenn A., Fischbein, Gustavo A., Pastini, Ana C., Ricci, Marcelo A., Coppari, Marcelo A., Toneguzzo, Fernando G.
• Granted Patent: US 8,685,451 B2
• Time in Patent Office: Days
• US Class Current: 424/473
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

This invention pertains to a multi-layered tablet for a triple combination release of active agents to an environment of use. More particularly, the invention pertains to a multi-layered tablet (1) comprising two external drug-containing layers (2 and 3) in stacked arrangement with respect to and on opposite sides of an oral dosage form (4) that provides a triple combination release of at least one active agent. In one embodiment of the invention the dosage form is an osmotic device. In another embodiment of the invention the dosage form is a gastro-resistant coated core. In yet another embodiment of the invention the dosage form is a matrix tablet. In a different embodiment the dosage form is a hard capsule.

Claims

1. A combination release tablet comprising:

a) a drug-containing rapid release first compressed composition comprising at least one drug;

b) a drug-containing extended release second compressed composition comprising at least one drug and a release rate modifier; and

c) a preformed and film-coated extended release intermediate drug-containing composition comprising a drug-containing core surrounded by a coating;

wherein the first compressed composition and second compressed composition oppose one another, are in direct contact with, in stacked arrangement with respect to, and disposed on opposite faces or surfaces of the intermediate drug-containing composition, whereby the tablet provides three different active agent release profiles.

2. The tablet of claim 1, wherein the preformed and film-coated extended release intermediate drug-containing composition is an osmotic device comprising a core surrounded by a membrane having a preformed passageway through it.

3. The tablet of claim 2, wherein the membrane is a semipermeable membrane, a microporous membrane, or an impermeable membrane.

4. The tablet of claim 3, wherein

(i) the preformed passageway is not plugged, or

(ii) the preformed passageway is plugged by the first or second compressed composition and initial release of drug from the core is delayed.

6. The tablet of claim 1, wherein the preformed and film-coated extended release intermediate drug-containing composition is a capsule comprising a shell enclosing a drug-containing composition.

7. The tablet of claim 6, wherein the shell comprises at least one preformed passageway.

8. The tablet of claim 7, wherein the shell is erodible, swellable, degradable and/or soluble in aqueous medium.

9. The tablet of claim 6, wherein the shell is erodible, swellable, degradable and/or soluble in aqueous medium and the drug-containing composition further comprises a release rate modifier.

10. The tablet of claim 6, wherein the shell is a release rate-controlling shell.

11. The tablet of claim 6, wherein the shell is not a release rate controlling shell and the drug-containing composition within the shell comprises a release rate-controlling material.

12. The tablet of claim 1, wherein the preformed and film-coated extended release intermediate drug-containing composition is a gastro-resistant coated core comprising a gastro-resistant coating surrounding a drug-containing composition.

13. The tablet of claim 12, wherein the core comprises a release rate-controlling material.

14. The tablet of claim 13, wherein the gastro-resistant coated core is adapted for release of drug downstream of the gastric region following oral administration of the tablet to a subject.

15. The tablet of claim 14, wherein

(i) the gastro-resistant coated core is adapted for release of drug in the intestine following oral administration of the tablet to a subject, or

(ii) the gastro-resistant coated core is adapted for release of drug in the colon following oral administration of the tablet to a subject.

17. The tablet of claim 1, wherein the tablet comprises three different drugs.

18. The tablet of claim 17, wherein a drug in the first compressed composition is different than a drug in the second compressed composition.

19. The tablet of claim 18, wherein

(i) a drug in the first compressed composition is different than a drug in the drug-containing core, or

(ii) the drug in the second compressed composition is different than the drug in the drug-containing core.

21. The tablet of claim 17, wherein

(i) the drug in the first compressed composition is the same as the drug in the drug-containing core,

(ii) the first compressed composition comprises two different drugs, the core comprises the third different drug, and the second compressed composition comprises a charge of either one of the three different drugs, or

(iii) the first compressed composition comprises a charge of each of two different drugs, the core comprises a charge of the third different drug, and the second compressed composition comprises an additional charge of either one of the three different drugs.

24. The tablet of claim 17, wherein the drug in the first compressed composition is the same as the drug in the second compressed composition.

25. The tablet of claim 24, wherein

(i) the drug in the first compressed composition is the same as the drug in the drug-containing core, or

(ii) the drug in the second compressed composition is different than the drug in the drug-containing core.

27. The tablet according to anyone of claims 2-4, wherein

(i) the rapid release first compressed composition comprises carbidopa and optionally levodopa;

the extended release second compressed composition comprises levodopa; and

the intermediate drug-containing composition comprises amantadine.

(ii) the rapid release first compressed composition comprises ondensetron;

the extended release second compressed composition comprises alprazolam; and

the intermediate drug-containing composition comprises venlafaxine,

(iii) the rapid release first compressed composition comprises carbidopa and optionally levodopa;

the extended release second compressed composition comprises levodopa; and

the intermediate drug-containing composition comprises ropinirole,

(iv) the rapid release first compressed composition comprises ondensetron;

the extended release second compressed composition comprises quetiapene; and

the intermediate drug-containing composition comprises venlafaxine,

(v) the rapid release first compressed composition comprises quetiapene;

the extended release second compressed composition comprises divalproex sodium; and

the intermediate drug-containing composition comprises lithium, or

(vi) the rapid release first compressed composition comprises ergotamine;

the extended release second compressed composition comprises naproxen; and

the intermediate drug-containing composition comprises domperidone.

32. The tablet according to anyone of claims 6-11, wherein

the rapid release first compressed composition comprises ondensetron;

the extended release second compressed composition comprises alprazolam; and

the intermediate drug-containing composition comprises venlafaxine.

33. The tablet of claims 12 or 13, wherein

(i) the rapid release first compressed composition comprises carbidopa and optionally levodopa;

the extended release second compressed composition comprises amantadine; and

the intermediate drug-containing composition comprises levodopa, or

(ii) the rapid release first compressed composition comprises carbidopa and optionally levodopa;

the extended release second compressed composition comprises entacapone; and

the intermediate drug-containing composition comprises levodopa.

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