Dosage forms and methods for providing effective reboxetine therapy with once-a-day dosing

• US 6,387,403 B1
• Filed: 09/14/2000
• Issued: 05/14/2002
• Est. Priority Date: 09/15/1999
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Bhatt, Padmanabh P., Edgren, David E., Desjardin, Michael A., Ayer, Atul D., Yam, Noymi V., Lam, Andrew C., Nixon, Phillip R., Seroff, Sylvia L.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Bennett, Rachel M.
• Application Number:
  US09/661,976
• Time in Patent Office: 607 Days
• Field of Search: 424/486, 424/464, 424/468, 424/473, 424/472
• US Class Current: 424/473
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Dosage forms and methods for providing sustained release of reboxetine are provided. The sustained release dosage forms provide therapeutically effective average steady-state plasma reboxetine concentrations when administered once per day. This once-a-day dosing regimen results in only one peak plasma reboxetine concentration occurrence in each 24 hour period. In addition, the peak plasma reboxetine concentration occurs at a later time following dose administration and exhibits a lesser magnitude than the peak plasma reboxetine concentration that occurs following administration of reboxetine in an immediate-release dosage form.

Claims

1. An osmotic dosage form adapted to release reboxetine at a uniform rate comprising:

a. a semipermeable membrane defining an internal compartment;

b. an osmotic composition component comprising reboxetine and a carbohydrate within the internal compartment; and

c. a delivery orifice formed or formable in the semipermeable membrane through which the reboxetine is delivered.

2. The dosage form of claim 1 wherein the uniform rate is over a prolonged period of time of about four hours or greater.

3. The dosage form of claim 1 wherein the uniform rate is at least about 0.2 mg/hr.

4. The dosage form of claim 1 wherein the release has a T₉₀ of at least about 8 hours.

5. The dosage form of claim 1 further comprising:

a sweilable polymer component within the internal compartment.

6. The dosage form described in claim 5 wherein the osmotic composition component and the swellable polymer component within the internal compartment are configured as adjacent layers and the delivery orifice is formed or formable through the semipermeable membrane at a location adjacent to the osmotic composition component.

7. The dosage form described in claim 5 further comprising a barrier layer separating the osmotic composition component and the swellable polymer component within the internal compartment and the delivery orifice being formed or formable through the semipermeable membrane at a location adjacent to the osmotic composition component.

8. The dosage form described in claim 7 further comprising an inner wall between the semipermeable membrane and the osmotic composition component, the barrier layer and the swellable polymer component, the delivery orifice being formed or formable through the semipermeable membrane and the inner wall at a location adjacent to the osmotic composition component.

18. The dosage form of claim 1 wherein the carbohydrate is selected from the group consisting of maltodextrin, lactose, dextrose, sucrose, mannitol, and sorbitol.

19. The dosage form of claim 18 comprising reboxetine and maltodextrin having a dextrose equivalence (DE) of 20 or less.

20. The dosage of claim 19 wherein the maltodextrin has a dextrose equivalence (DE) of 9-20.

21. The dosage form of claim 1 formed as a tablet compressed under a force of 3500 newtons or greater.

9. A method of treating a condition in a subject responsive to reboxetine, the method comprising orally administering to the subject an osmotic dosage form adapted to release reboxetine at a uniform rate comprising:

a. a semipermeable membrane defining an Internal compartment;

b. an osmotic composition component comprising reboxetine and a carbohydrate within the internal compartment; and

c. a delivery orifice formed or formable in the semipermeable membrane through which the reboxetine is delivered.

10. The method of claim 9 wherein the uniform rate is over a prolonged period of time of about four hours or greater.

11. The method of claim 9 wherein the uniform rate is at least about 0.2 mg/hr.

12. The method of claim 9 wherein the release has a T₉₀ of at least about 8 hours.

13. The method of claim 9 wherein the dosage form is administered once a day.

14. The method of claim 13 further comprising producing a therapeutically effective average steady-state plasma reboxetine concentration.

15. The method of claim 9 further comprising producing a steady-state peak plasma reboxetine concentration at a time at least 4 hours following dose administration.

16. The method of claim 9 further comprising producing one peak plasma reboxetine concentration during each 24-hour period.

17. The method of claim 9 further comprising providing steady-state C_max/dose ratios of less than about 30 and more preferably less than about 25.