Osmotic device containing venlafaxine and an anti-psychotic agent

• US 6,572,890 B2
• Filed: 11/30/2000
• Issued: 06/03/2003
• Est. Priority Date: 01/13/2000
• Status: Expired due to Term

• Current Assignee: Osmotica Kereskedelmi Es Szolgaltato Kft (Osmotica Pharmaceuticals Plc)
• Original Assignee: Osmotica Corp.
• Inventors: Faour, Joaquina, Vergez, Juan
• Primary Examiner(s): Dees, Jose′ G.
• Assistant Examiner(s): DeWitty, Robert M
• Application Number:
  US09/728,276
• Publication Number:
  US 20010048943A1
• Time in Patent Office: 915 Days
• Field of Search: 514/220, 514/380, 424/468, 424/473
• US Class Current: 424/473
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

The present invention provides an osmotic device containing controlled release venlafaxine in the core in combination with an anti-psychotic agent in a rapid release external coat. A wide range of anti-psychotic agents can be used in this device. Particular embodiments of the invention provide osmotic devices having predetermined release profiles. One embodiment of the osmotic device includes an external coat that has been spray-coated rather compression-coated onto the device. The device with spray-coated external core is smaller and easier to swallow than the similar device having a compression-coated external coat. The device is useful for the treatment of depression, anxiety or psychosis related disorders.

Claims

1. A controlled release dosage form comprising a first composition comprising a therapeutically effective amount of venlafaxine, and a second composition comprising a therapeutically effective amount of an anti-psychotic agent, wherein the dosage form provides a controlled release of venlafaxine and an immediate release of the anti-psychotic agent, and wherein at least 75% of the anti-psychotic agent is released within about 1 hour after exposure of the dosage form to an aqueous solution, and at least 60% of the venlafaxine is released in a controlled manner within about 10 hours after exposure of the dosage form to an aqueous solution.

2. The dosage form of claim 1, wherein the release of at least one of the venlafaxine and the anti-psychotic agent has a delayed onset.

3. The dosage form of claim 1, wherein the dosage form delivers the anti-psychotic agent to the upper GI tract and the venlafaxine to the middle to lower GI tract of an animal to which it is administered orally.

4. The dosage form of claim 1, wherein the dosage form provides a venlafaxine C_max of about 17-23 ng/ml of plasma when administered orally to a mammal.

5. The dosage form of claim 4, wherein the dosage form provides a venlafaxine T_max at about 7-11 hours after oral administration.

6. The dosage form of claim 1, wherein the dosage form provides a venlafaxine dissolution profile as follows when exposed to an aqueous environment:

7. The dosage form of claim 1, wherein the dosage form provides a venlafaxine C_max of about 20-27 ng/ml of plasma when administered orally to a mammal.

8. The dosage form of claim 7, wherein the dosage form provides a venlafaxine T_max at about 3.5-8.5 hours after oral administration.

9. The osmotic device of claim 1, wherein the dosage form provides a single-dose venlafaxine plasma concentration profile in a mammal as follows:

10. The osmotic device of claim 1, wherein the osmotic device provides a single-dose venlafaxine plasma concentration profile in a mammal as follows:

11. The dosage form of any one of claims 1, or 2-10, wherein the anti-psychotic agent is selected from the group consisting of risperidone, olanzapine, clozapine, sertindole, ziprasidone, quetiapine, sulpiride, pimozide, clothiapine, molindone, loxapine, trifluoperazine, haloperidol, flupenthixol, chlorpromazine, chlorprothixene, clopenthixol, droperidol, perphenazine, fluphenazine, lithium, mesoridazine, spiperone, promazine, prochlorperazine, thioridazine, thiothixene, triflupromazine and raclopride.

12. A controlled release dosage form comprising a first composition comprising a therapeutically effective amount of venlafaxine, and a second composition comprising a therapeutically effective amount of an anti-psychotic agent, wherein the dosage form provides a controlled release of venlafaxine and an immediate release of the anti-psychotic agent;

at least 60% of the venlafaxine is released in a controlled manner within about 10 hours after exposure of the dosage form to an aqueous solution;

at least 75% of the anti-psychotic agent is released within about 1 hour after exposure of the dosage form to an aqueous solution; and

the release of at least one of the venlafaxine and the anti-psychotic agent has a delayed onset.

13. The dosage form of claim 12, wherein the dosage form delivers the anti-psychotic agent to the upper GI tract and the venlafaxine to the middle to lower GI tract.

14. The dosage form of claim 12, wherein the dosage form provides a venlafaxine C_max of about 17-23 ng/ml of plasma when administered to a mammal.

15. The dosage form of claim 14, wherein the dosage form provides a venlafaxine T_max at about 7-11 hours after administration.

16. The dosage form of claim 12, wherein the dosage form provides a venlafaxine C_max of about 20-27 ng/ml of plasma when administered to a mammal.

17. The dosage form of claim 16, wherein the dosage form provides a venlafaxine T_max at about 3.5-8.5 hours after administration.

18. The dosage form of any one of claims 12,13-17, wherein the anti-psychotic agent is selected from the group consisting of risperidone, olanzapine, clozapine, sertindole, ziprasidone, quetiapine, sulpiride, pimozide, clothiapine, molindone, loxapine, trifluoperazine, haloperidol, flupenthixol, chlorpromazine, chlorprothixene, clopenthixol, droperidol, perphenazine, fluphenazine, lithium, mesoridazine, spiperone, promazine, prochlorperazine, thioridazine, thiothixene, triflupromazine and raclopride.

19. A controlled release dosage form comprising a first composition comprising a therapeutically effective amount of venlafaxine, and a second composition comprising a therapeutically effective amount of an anti-psychotic agent, wherein the dosage form provides a controlled release of venlafaxine and an immediate release of the anti-psychotic agent;

at least 60% of the venlafaxine is released in a controlled manner within about 10 hours after exposure of the dosage form to an aqueous solution;

at least 75% of the anti-psychotic agent is released within about 1 hour after exposure of the dosage form to an aqueous solution;

the release of at least one of the venlafaxine and the anti-psychotic agent has a delayed onset; and

the dosage form provides a venlafaxine C_max of about 17-23 ng/ml of plasma when administered to a mammal.

20. The dosage form of claim 19, wherein the dosage form provides a venlafaxine T_max about 7-11 hours after administration.

23. The dosage form of any one of claims 19-22, wherein the anti-psychotic agent is selected from the group consisting of risperidone, olanzapine, clozapine, sertindole, ziprasidone, quetiapine, sulpiride, pimozide, clothiapine, molindone, loxapine, trifluoperazine, haloperidol, flupenthixol, chlorpromazine, chlorprothixene, clopenthixol, droperidol, perphenazine, fluphenazine, lithium, mesoridazine, spiperone, promazine, prochlorperazine, thioridazine, thiothixene, triflupromazine and raclopride.

21. A controlled release dosage form comprising a first composition comprising a therapeutically effective amount of venlafaxine, and a second composition comprising a therapeutically effective amount of an anti-psychotic agent, wherein the dosage form provides a controlled release of venlafaxine and an immediate release of the anti-psychotic agent;

at least 60% of the venlafaxine is released in a controlled manner within about 10 hours after exposure of the dosage form to an aqueous solution;

at least 75% of the anti-psychotic agent is released within about 1 hour after exposure of the dosage form to an aqueous solution;

the release of at least one of the venlafaxine and the anti-psychotic agent has a delayed onset; and

the dosage form provides a venlafaxine C_max of about 20-27 ng/ml of plasma when administered to a mammal.

22. The dosage form of claim 21, wherein the dosage form provides a venlafaxine T_max about 3.5-8.5 hours after administration.