Methods and dosage forms for controlled delivery of oxycodone

• US 20040010000A1
• Filed: 04/25/2003
• Published: 01/15/2004
• Est. Priority Date: 04/29/2002
• Status: Abandoned Application

• Current Assignee: Atul D. Ayer, Clark P. Allphin, Deborah J. Johnson, Linda M. Hearney, Michael A. Desjardin, Nishit B. Modi, Padmaja Shivanand, Sonya Seroff, Tracy A. Fink
• Original Assignee: Atul D. Ayer, Clark P. Allphin, Deborah J. Johnson, Linda M. Hearney, Michael A. Desjardin, Nishit B. Modi, Padmaja Shivanand, Sonya Seroff, Tracy A. Fink
• Inventors: Fink, Tracy A., Johnson, Deborah J., Hearney, Linda M., DesJardin, Michael A., Seroff, Sonya, Ayer, Atul D., Shivanand, Padmaja, Allphin, Clark P., Modi, Nishit B.
• Application Number:
  US10/423,454
• Publication Number:
  US 20040010000A1
• Time in Patent Office: Days
• US Class Current: 514/282
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

Dosage forms and methods for the controlled release of oxycodone over a prolonged period of time are described. The sustained release dosage forms provide therapeutically effective average steady-state plasma oxycodone concentrations when administered once per day. This once-a-day dosing regimen results in only one peak plasma oxycodone concentration occurrence in each 24 hour period that occurs at a later time after administration and exhibits a lesser magnitude than the peak plasma oxycodone concentration that occurs following administration of oxycodone in an immediate-release dosage form and other prior art extended release dosage forms.

Claims

1. A sustained release oral dosage form for once-a-day controlled delivery of oxycodone comprising:

(a) a core which comprises;

(i) an osmotic agent; and

(ii) oxycodone and/or one or more pharmaceutically-acceptable acid addition salts thereof (the compound);

(b) a semipermeable membrane enveloping the core; and

(c) an exit orifice through the semipermeable membrane which communicates with the core so as to allow release of the compound to the environment;

wherein the dosage form releases the compound over a prolonged period of time at a uniform rate of release such that the average hourly release rate from the core varies positively or negatively by no more than about 30% from either the preceding or the subsequent average hourly release rate during a period of time Δ

T_uniform which begins with the time when the cumulative release of the compound from the core reaches about 25% and which ends with the time when the cumulative release of the compound from the core reaches 75%.

2. The dosage form of claim 1 wherein the average hourly release rate from the core varies positively or negatively by no more than about 25% from either the preceding or the subsequent average hourly release rate during Δ

T_uniform.

3. The dosage form of claim 1 wherein the average hourly release rate from the core varies positively or negatively by no more than about 10% from either the preceding or the subsequent average hourly release rate during Δ

T_uniform.

4. The dosage form of claim 1 wherein Δ

T_uniform is at least about 4 hours.

5. The dosage form of claim 1 wherein Δ

T_uniform is greater than or equal to about 6 hours.

6. The dosage form of claim 1 wherein Δ

T_uniform is greater than or equal to about 10 hours.

7. The dosage form of claim 1 wherein the dosage form has a T₇₀ value which is at least about 10 hours.

8. The dosage form of claim 1 wherein the dosage form has a T₇₀ value which is greater than or equal to about 15 hours.

9. The dosage form of claim 1 wherein the dosage form has a T₇₀ value which is greater than or equal to about 17 hours.

10. The dosage form of claim 1 wherein the core comprises a polyalkylene oxide.

11. The dosage form of claim 1 wherein the core comprises:

(i) a first drug layer which comprises the compound, and

(ii) a second expandable layer which comprises the osmotic agent and does not comprise the compound.

12. The dosage form of claim 1 further comprising an immediate release coating which comprises the compound.

13. A method of treating a condition in a subject responsive to the administration of oxycodone comprising orally administering the dosage form of claim 1 or claim 12 to the subject.

14. The method of claim 13 wherein the administration of the dosage form on a once-a-day basis provides a mean, steady state, plasma concentration profile which for a 24 hour period commencing with an administration of said dosage form has a maximum value C_max which occurs at greater than 6 hours after said administration.

15. The method of claim 14 wherein C_max occurs at greater than 12 hours after said administration.

16. The method of claim 14 wherein C_max occurs at greater than 15 hours after said administration.

17. The method of claim 13 wherein the administration of the dosage form on a once-a-day basis provides a mean, steady state, plasma concentration profile which for a 24 hour period commencing with an administration of said dosage form has a maximum value C_max which satisfies the relationship:

C_max/D<

30,

where C_max is measured in nanograms/milliliter and D is the amount of compound in the dosage form measured in milligrams.

18. The method of claim 17 wherein C_max/D<

25.

19. The method of claim 13 wherein the administration of the dosage form on a once-a-day basis provides a mean, steady state, plasma concentration profile which for a 24 hour period commencing with an administration of said dosage form has a maximum value C_max and a 24-hour value C₂₄ which satisfy the relationship:

C_max<

2·

C₂₄.

20. The method of claim 13 wherein the administration of the dosage form on a once-a-day basis provides a mean, steady state, plasma concentration profile which for a 24 hour period commencing with an administration of said dosage form has minimum and maximum values C_min and C_max which satisfy the relationship:

(C_max−

C_min)/C_min<

2.

21. The method of claim 13 wherein the administration of the dosage form on a once-a-day basis provides a mean, steady state, plasma concentration profile which for a 24 hour period commencing with an administration of said dosage form has concentration values that lie between about 5 ng/ml and about 10 ng/ml when the dosage form contains 20 mg of the compound.