Granted Patent B2

US 12,246,094 · App. 18/603,884 · Granted Mar 11, 2025

Inventors: William H. McKenna (Yonkers, NY); Richard O. Mannion (Furlong, PA); Edward P. O'Donnell (Basking Ridge, NJ); Haiyong H. Huang (Princeton, NJ)

Assignees: PURDUE PHARMA L.P.; PURDUE PHARMACEUTICALS L.P.

A61K9/28A61J3/005A61J3/06A61J3/10A61K9/0002A61K9/0053A61K9/1641A61K9/2013A61K9/2018A61K9/2027A61K9/2031A61K9/2054A61K9/2077A61K9/209A61K9/2095A61K9/284A61K9/2853A61K9/2866A61K9/2893A61K31/485A61K45/06A61K47/10A61K47/34B29B7/02B29B7/88B29C35/045B29C35/16B29C37/0025B29C43/003B29C43/02B29C43/52B29C71/00B29C71/009A61K9/2072B29C2035/046B29C2035/1658B29K2071/02B29K2105/0035B29K2105/251B29K2995/0088B29L2031/753

Abstract

Claims (27)

1. A solid oral extended release dosage form, comprising:

a shaped extended release matrix comprising from about 10 mg to about 160 mg oxycodone or a pharmaceutically acceptable salt thereof, and polyethylene oxide (PEO) having an approximate molecular weight of 4 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 convection heated in a coating pan for a time period of at least about 5 minutes at a temperature of at least about 60° C. and thereafter cooled, 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 ), and

wherein the dosage form provides a mean maximum plasma concentration (C max ) of oxycodone from about 6 ng/mL to about 240 ng/mL.

2. The solid oral extended release dosage form of claim 1 , wherein a plurality of convection heated particles of PEO adhere to or fuse with each other within the matrix.

3. The solid oral extended release dosage form of claim 1 , wherein the shaped extended release matrix further comprises magnesium stearate.

4. The solid oral extended release dosage form of claim 1 , wherein the dosage form provides a 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.

5. 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.

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

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

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

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

10. 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.

11. 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.

12. The solid oral extended release dosage form of claim 1 , comprising oxycodone hydrochloride.

13. The solid oral extended release dosage form of claim 1 , that provides a mean t max of oxycodone at about 2 to about 6 hours.

14. The solid oral extended release dosage form of claim 1 , further comprising a PEO having an approximate molecular weight of 100,000 Da to 900,000 Da based on rheological measurements.

15. 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.

16. 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.

17. A solid oral extended release dosage form comprising: an extended release matrix comprising from about 10 mg to about 160 mg oxycodone hydrochloride, 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 dosage form provides 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 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 ); wherein the extended release matrix is shaped to form a tablet and convection heated in a coating pan for a time period of at least about 5 minutes at a temperature of at least about 60° C. and thereafter cooled.

18. A solid oral extended release dosage form comprising: an extended release matrix comprising oxycodone hydrochloride, 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 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 hydrochloride 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 and wherein the density of the 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 ); wherein the extended release matrix is shaped to form a tablet and convection heated in a coating pan for a time period of at least about 5 minutes at a temperature of at least about 60° C. and thereafter cooled.

19. A solid oral extended release dosage form, comprising:

a shaped extended release matrix comprising oxycodone hydrochloride, 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 convection heated in a coating pan for a time period of at least about 5 minutes at a temperature of at least about 60° C. and thereafter cooled,

wherein the dosage form provides a 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 hydrochloride released after 1 hour, between 25 and 65% (by wt) oxycodone hydrochloride released after 2 hours, between 45 and 85% (by wt) oxycodone hydrochloride released after 4 hours and between 55 and 95% (by wt) oxycodone hydrochloride released after 6 hours, and

wherein the density of the 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 ).

Assignments (3)

Continuity (16)

References Cited (400)