Tamper resistant dosage forms

Patent metadata

Field	Value
Publication number	US-12280152-B2
Application number	US-202418953603-A
Country	US
Kind code	B2
Filing date	Nov 20, 2024
Priority date	Aug 25, 2006
Publication date	Apr 22, 2025
Grant date	Apr 22, 2025

Abstract

The present invention relates to pharmaceutical dosage forms, for example to a tamper resistant dosage form including an opioid analgesic, and processes of manufacture, uses, and methods of treatment thereof.

First claim

The invention claimed is:

1. A solid oral extended release dosage form, comprising:
a shaped extended release matrix comprising oxycodone or a pharmaceutically acceptable salt thereof, magnesium stearate and polyethylene oxide (PEO) having an approximate molecular weight of 2 million Da to 15 million Da based on rheological measurements, wherein the PEO comprises at least about 30% (by weight) of the total weight of the dosage form;
wherein the extended release matrix is shaped to form a tablet and cured by subjecting a bed of free flowing tablets to a temperature of at least about 60° C. for a time period of at least about 5 minutes and thereafter cooling the bed;
wherein the extended release matrix is film coated;
wherein the dosage form comprises about 10 mg, about 15 mg, about 20 mg, about 30 mg, about 40 mg, about 60 mg or about 80 mg oxycodone or a pharmaceutically acceptable salt thereof;
wherein the density of the shaped extended release matrix is equal to or less than about 1.20 g/cm 3 as determined by Archimedes Principle using a liquid of known density (ρ 0 ); and
wherein the extended release dosage form provides a mean t max of oxycodone at about 2 to about 6 hours.

2. The solid oral extended release dosage form of claim 1 , wherein the bed of free flowing tablets is cured in a coating pan.

3. The solid oral extended release dosage form of claim 1 , wherein the bed of free flowing tablets is cured in a fluidized bed.

4. The solid oral extended release dosage form of claim 1 , wherein the tablets are film coated prior to curing.

5. The solid oral extended release dosage form of claim 1 , wherein the tablets are film coated after curing.

6. The solid oral extended release dosage form of claim 1 , wherein the tablets are film coated prior to curing and after curing.

7. The solid oral extended release dosage form of claim 1 , wherein the PEO has an approximate molecular weight of 2 million Da to 8 million Da based on rheological measurements.

8. The solid oral extended release dosage form of claim 1 , wherein the dosage form provides an in-vitro dissolution rate, which when measured in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C., is between 12.5 and 55% (by wt) oxycodone or pharmaceutically acceptable salt thereof released after 1 hour, between 25 and 65% (by wt) oxycodone or pharmaceutically acceptable salt thereof released after 2 hours, between 45 and 85% (by wt) oxycodone or pharmaceutically acceptable salt thereof released after 4 hours and between 55 and 95% (by wt) oxycodone or pharmaceutically acceptable salt thereof released after 6 hours.

9. The solid oral extended release dosage form of claim 1 , wherein the dosage form provides an in-vitro dissolution rate, when measured in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) comprising 40% ethanol at 37° C., characterized by the percent amount of oxycodone or pharmaceutically acceptable salt thereof released at 0.5 hours, that deviates no more than about 20% points 0.5 hours from the corresponding in-vitro dissolution rate measured in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C. without ethanol.

10. The solid oral extended release dosage form of claim 1 , wherein the temperature is from about 62° C. to about 90° C.

11. The solid oral extended release dosage form of claim 1 , wherein the temperature is from about 68° C. to about 85° C.

12. The solid oral extended release dosage form of claim 1 , wherein the time period is from about 15 minutes to about 10 hours.

13. The solid oral extended release dosage form of claim 1 , wherein the time period is from about 30 minutes to about 4 hours.

14. The solid oral extended release dosage form of claim 1 , when subjected to a maximum force of about 196 N or about 439 N in a tablet hardness test, does not break.

15. The solid oral extended release dosage form of claim 1 , wherein the tablet when subjected to an indentation test resists a work of at least about 0.06 J without cracking.

16. The solid oral extended release dosage form of claim 1 , wherein the dosage form provides a mean maximum plasma concentration (C max ) of oxycodone from about 6 ng/mL to about 240 ng/mL.

17. The solid oral extended release dosage form of claim 1 , wherein the total amount of PEO comprises at least about 65% (by wt) of the total weight of the dosage form.

18. The solid oral extended release dosage form of claim 1 , wherein the total amount of PEO comprises at least about 80% (by wt) of the total weight of the dosage form.

19. A solid oral extended release dosage form, comprising:
a shaped extended release matrix comprising oxycodone or a pharmaceutically acceptable salt thereof, magnesium stearate and polyethylene oxide (PEO) having an approximate molecular weight of 2 million Da to 15 million Da based on rheological measurements, wherein the PEO comprises at least about 30% (by weight) of the total weight of the dosage form;
wherein the extended release matrix is shaped to form a tablet and cured by subjecting a bed of free flowing tablets to a temperature of at least about 60° C. for a time period of at least about 5 minutes and thereafter cooling the bed;
wherein the extended release matrix is film coated;
wherein the dosage form comprises about 10 mg, about 15 mg, about 20 mg, about 30 mg, about 40 mg, about 60 mg or about 80 mg oxycodone or a pharmaceutically acceptable salt thereof and provides a mean t max of oxycodone at about 2 to about 6 hours and a mean maximum plasma concentration (C max ) of oxycodone from about 6 ng/ml to about 240 ng/mL; and
wherein the density of the shaped extended release matrix is equal to or less than about 1.20 g/cm 3 as determined by Archimedes Principle using a liquid of known density (ρ 0 ).

20. The solid oral extended release dosage form of claim 19 , wherein the bed of free flowing tablets is cured in a coating pan.

21. The solid oral extended release dosage form of claim 19 , wherein the bed of free flowing tablets is cured in a fluidized bed.

22. The solid oral extended release dosage form of claim 19 , wherein the tablets are film coated prior to curing.

23. The solid oral extended release dosage form of claim 19 , wherein the tablets are film coated after curing.

24. The solid oral extended release dosage form of claim 19 , wherein the tablets are film coated prior to curing and after curing.

Assignees

• Purdue Pharma Lp
• Purdue Pharmaceuticals LP

Inventors

• Mckenna William H
• Mannion Richard O
• O'Donnell Edward P
• Huang Haiyong H

Classifications

• B29K2995/0088

  Molecular weight · CPC title

• B29C71/00

  After-treatment of articles without altering their shape; Apparatus therefor (B29C44/56, B29C73/00 take precedence; surface shaping B29C59/00 {; for joined or sealed parts B29C66/03; after-treatment specially adapted for vulcanising tyres B29D30/0633}) · CPC title

• B29K2105/251

  Particles, powder or granules (expandable particles B29K2105/046) · CPC title

• A61K9/2027

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K9/284

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone · CPC title