Abuse-resistant controlled-release opioid dosage form

Patent metadata

Field	Value
Publication number	US-2016256456-A1
Application number	US-201615159465-A
Country	US
Kind code	A1
Filing date	May 19, 2016
Priority date	May 11, 2001
Publication date	Sep 8, 2016
Grant date	—

Abstract

Abuse-resistant, controlled release opioid tablets are a combination containing an opioid antagonist such as naloxone at a level above that needed to suppress the euphoric effect of the opioid, if the combination were crushed to break the controlled release properties causing the opioid and opioid antagonist to be released as a immediate release product as a single dose. The controlled release nature of the table prevents the accumulation of orally effective amounts of opioid antagonist when taken normally. The opioid antagonist is contained in a controlled-release matrix and released, over time, with the opioid.

First claim

1 - 4 . (canceled)

5 . A method of preventing abuse of an oral opioid pharmaceutical composition, comprising providing a therapeutically effective amount of an oral controlled release pharmaceutical composition comprising:
oxycodone and naloxone, wherein the oxycodone and the naloxone are present in the pharmaceutical composition in a ratio of 5:1 to 1:1; and wherein the pharmaceutical composition releases the naloxone and the oxycodone such that at least 87.5% of the naloxone is released from the composition over 8-12 hours.

6 . The method of claim 5 , wherein the oxycodone is present in the pharmaceutical composition in an amount of 10-160 mg.

7 . The method of claim 5 , wherein the oxycodone is present in the pharmaceutical composition in an amount of 10-80 mg.

8 . The method of claim 5 , wherein the oxycodone is present in the pharmaceutical composition in an amount of 10-40 mg.

9 . The method of claim 5 , wherein the oxycodone is present in the pharmaceutical composition in an amount of 10 mg and the naloxone is present in an amount of 2-10 mg.

10 . The method of claim 5 , wherein the oxycodone is present in the pharmaceutical composition in an amount of 20 mg and the naloxone is present in an amount of 5-20 mg.

11 . The method of claim 5 , wherein the oxycodone is present in the pharmaceutical composition in an amount of 40 mg and the naloxone is present in an amount of 8-40 mg.

12 . The method of claim 5 , wherein the oxycodone is present in the pharmaceutical composition in an amount of 80 mg and the naloxone is present in an amount of 16-80 mg.

13 . The method of claim 5 , wherein the naloxone is present in the pharmaceutical composition in an amount of 2-160 mg.

14 . The method of claim 5 , wherein the naloxone is present in the pharmaceutical composition in an amount of 2-40 mg.

15 . The method of claim 5 , wherein the naloxone is present in the pharmaceutical composition in an amount of 5-20 mg.

16 . The method of claim 5 , wherein the oxycodone and the naloxone are present in the pharmaceutical composition in a ratio of 4:1 to 1:1.

17 . The method of claim 5 , wherein the oxycodone is in the form of oxycodone hydrochloride.

18 . The method of claim 5 , wherein the naloxone is in the form of a pharmaceutically acceptable salt thereof.

19 . The method of claim 5 , wherein the release rate of the naloxone from the pharmaceutical composition is approximately 100 percent to approximately 25 percent of the release rate of the oxycodone.

20 . The method of claim 5 , wherein the release rate of the naloxone from the pharmaceutical composition is approximately 100 percent of the release rate of the oxycodone.

21 . The method of claim 5 , wherein >90% of the naloxone is released from the pharmaceutical composition over 10 hours.

22 . The method of claim 5 , wherein the oxycodone and the naloxone are released from the prepared pharmaceutical composition over a period greater than 4 hours.

23 . The method of claim 5 , wherein the pharmaceutical composition further comprises a controlled release matrix that contains the oxycodone and the naloxone.

24 . The method of claim 5 , wherein the pharmaceutical composition is in the form of a tablet.

25 . The method of claim 5 , wherein the naloxone is not readily separable from the oxycodone in the pharmaceutical composition.

26 . The method of claim 5 , wherein sufficient naloxone is released to block the opioid euphoric effect when the pharmaceutical composition is crushed.

27 . The method of claim 5 , wherein the naloxone is released as immediate release capable of inducing withdrawal in dependent individuals if the pharmaceutical composition is crushed and the controlled release properties broken.

28 . The method of claim 5 , wherein the naloxone is released at a rate ineffective for inducing withdrawal when the pharmaceutical composition is taken orally in intact form.

29 . The method of claim 5 , wherein the release of the naloxone does not block the action of the oxycodone when the controlled release properties of the pharmaceutical composition are intact.

30 . The method of claim 5 , wherein the method prevents oral abuse of the oral opioid pharmaceutical composition.

31 . The method of claim 5 , wherein the abuse comprises crushing the pharmaceutical composition.

32 . A method of preventing oral abuse of an oral opioid pharmaceutical composition, comprising providing a therapeutically effective amount of an oral controlled release pharmaceutical composition comprising:
oxycodone hydrochloride and a pharmaceutically acceptable salt of naloxone; wherein 2-40 mg of the pharmaceutically acceptable salt of naloxone is present in the pharmaceutical composition; wherein the oxycodone hydrochloride and the pharmaceutically acceptable salt of naloxone are present in the pharmaceutical composition in a ratio of 4:1 to 1:1; wherein the pharmaceutical composition further comprises a controlled release matrix that contains the oxycodone and the naloxone; wherein the pharmaceutical composition releases the pharmaceutically acceptable salt of naloxone and the oxycodone hydrochloride such that at least 87.5% of the pharmaceutically acceptable salt of naloxone is released from the composition over 8-12 hours.

33 . The method of claim 32 , wherein the oxycodone is present in the pharmaceutical composition in an amount of 10, 20, 40, or 80 mg.

34 . The method of claim 32 , wherein the matrix comprises a methacrylate copolymer.

Assignees

• Purdue Pharma Lp

Inventors

• Caruso Frank S
• Kao Huai-Hung

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title

• A61K31/485 Primary

  Morphinan derivatives, e.g. morphine, codeine · CPC title

• A61K9/20

  Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)} · CPC title