ONCE-A-DAY OXYCODONE FORMULATIONS
The invention is directed to sustained release formulations containing oxycodone or a pharmaceutically acceptable salt thereof which provide a mean C 24 /C max oxycodone ratio of 0.6 to 1.0 or 0.7 to 1 after oral administration at steady state to patients and methods thereof.
1 - 22 . (canceled)
23 . A sustained release oral dosage form comprising:
(a) a bilayer core comprising:
(i) a drug layer comprising an analgesically effective amount of oxycodone or a pharmaceutically acceptable salt thereof; and
(ii) a displacement layer comprising an osmopolymer; and
(b) a semipermeable wall surrounding the bilayer core having a passageway disposed therein for the release of said oxycodone or pharmaceutically acceptable salt thereof;
said dosage form providing an analgesic effect for at least about 24 hours after steady-state oral administration to human patients; and
said dosage form providing a mean C 24 /C max oxycodone ratio of 0.6 to 1.0 after oral administration at steady state to said patients.
24 . The dosage form of claim 23 , which provides a mean T max of oxycodone in about 2 to about 17 hours after administration at steady state to said patients.
25 . The dosage form of claim 23 , which provides a mean T max of oxycodone in about 8 to about 16 hours after administration at steady state to said patients.
26 . The dosage form of claim 23 , which provides a mean W 50 of the oxycodone of between 4 and 24 hours after administration at steady state to said patients.
27 . The dosage form of claim 23 , which provides a W 50 of the oxycodone of at least 12 hours after administration at steady state to said patients.
28 . The dosage form of claim 23 , wherein said displacement layer further comprises an osmagent.
29 . The dosage form of claim 28 , wherein said osmagent is selected from the group consisting of osmotic salts and osmotic carbohydrates.
30 . The dosage form of claim 23 , wherein said pharmaceutically acceptable salt of oxycodone is oxycodone hydrochloride.
31 . The dosage form of claim 23 , wherein said oxycodone or pharmaceutically acceptable salt thereof is in an amount of from about 5 to about 640 mg.
32 . The dosage form of claim 23 , which provides a mean T max of oxycodone which occurs at about 12 to about 16 hours after administration at steady state to said patients.
33 . The dosage form of claim 23 , which provides a mean C 24 /C max ratio of 0.7 to 0.99 after administration at steady state to said patients.
34 . The dosage form of claim 23 , which provides a mean C 24 /C max ratio of 0.8 to 0.95 after administration at steady state to said patients.
35 . The dosage form of claim 23 , which provides an in-vitro release rate, of oxycodone or a pharmaceutically acceptable salt thereof, when measured by the USP Basket Method at 100 rpm in 900 ml aqueous buffer at a pH of between 1.6 and 7.2 at 37° C. of from 0% to about 40% at 1 hour, from about 8% to about 70% at 4 hours, from about 20% to about 80% at 8 hours, from about 30% to about 95% at 12 hours, from about 35% to about 95% at 18 hrs, and greater than about 50% at 24 hours.
36 . A method of treating pain in patients comprising:
orally administering to human patients a sustained release oral dosage form comprising
(a) a bilayer core comprising:
(i) a drug layer comprising an analgesically effective amount of oxycodone or a pharmaceutically acceptable salt thereof; and
(ii) a displacement layer comprising an osmopolymer; and
(b) a semipermeable wall surrounding the bilayer core having a passageway disposed therein for the release of said oxycodone or pharmaceutically acceptable salt thereof;
to provide an analgesic effect at least about 24 hours after oral administration at steady state to human patients; and to provide a mean C 24 /C max oxycodone ratio of 0.6 to 1.0 after oral administration at steady state to said patients.
37 . The method of claim 36 , which provides a mean T max of oxycodone at about 2 to about 17 hours after administration at steady state to said patients.
38 . The method of claim 36 , which provides a mean T max of oxycodone at about 8 to about 16 hours after administration at steady state to said patients.
39 . The method of claim 36 , which provides a W 50 of the oxycodone of between 4 and 24 hours after administration at steady state to said patients.
40 . The method of claim 39 , which provides a W 50 of the oxycodone of at least 12 hours after administration at steady state to said patients.
41 . The method of claim 36 , which provides a mean C 24 /C max ratio of 0.7 to 0.99 after administration at steady state to said patients.
42 . The method of claim 36 , which provides a mean C 24 /C max ratio of 0.8 to 0.95 after administration at steady state to said patients.
43 . The method of claim 36 , wherein said dosage form provides an in-vitro release rate of oxycodone or a pharmaceutically acceptable salt thereof, when measured by the USP Basket Method at 100 rpm in 900 ml aqueous buffer at a pH of between 1.6 and 7.2 at 37° C. of from 0% to about 40% at 1 hour, from about 8% to about 70% at 4 hours, from about 20% to about 80% at 8 hours, from about 30% to about 95% at 12 hours, from about 35% to about 95% at 18 hrs, and greater than about 50% at 24 hours.
44 - 71 . (canceled)
72 . The dosage form of claim 23 , which is overcoated with an additional amount of oxycodone or a pharmaceutically acceptable salt thereof in an immediate release form.
73 . An osmotic dosage form comprising
a homogeneous core comprising oxycodone or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable polymer; and
a semipermeable membrane having a passageway, the semipermeable membrane surrounding the homogeneous core;
wherein the dosage form provides an analgesic effect for at least about 24 hours and a mean C 24 /C max oxycodone ratio of 0.7 to 1 after steady-state oral administration to human patients.
74 . The dosage form of claim 73 , which is overcoated with additional oxycodone and pharmaceutically acceptable salt thereof in an immediate release form.
75 . The dosage form of claim 73 , wherein the pharmaceutically acceptable polymer is polyethylene oxide.
76 . The dosage form of claim 73 , further comprising a disintegrant.
77 . The dosage form of claim 73 , further comprising an absorption enhancer.
78 . The dosage form of claim 73 , wherein the semipermeable membrane comprises a poly(cellulose) with a number-average molecular weight of 20,000 to 7,500,000.
79 . The dosage form of claim 78 , wherein the poly(cellulose) is selected from the group consisting of a cellulose ester polymer, a cellulose ether polymer and cellulose ester-ether polymer.
80 . An osmotic dosage form comprising:
1 to 640 mg of oxycodone or a pharmaceutically acceptable salt thereof,
25 to 500 mg of poly(alkylene oxide having a 150,000 to 500,000 average molecular weight,
1 to 50 mg of polyvinylpyrrolidone) having a 40,000 average molecular weight, and
0 to about 7.5 mg of a lubricant,
wherein the dosage form provides an analgesic effect for at least about 24 hours and a mean C 24 /C max oxycodone ratio of 0.7 to 1 after steady-state oral administration to human patients.