Composition and dosage form comprising opioid antagonist

• US 5,866,164 A
• Filed: 03/12/1997
• Issued: 02/02/1999
• Est. Priority Date: 03/12/1996
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Barclay, Glen E., Rodriguez, Susan, Kuczynski, Anthony L., Merrill, Sonya, Childers, Jerry D.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Shelborne, Kathryne E.
• Application Number:
  US08/815,769
• Time in Patent Office: 692 Days
• Field of Search: 424/472, 424/473
• US Class Current: 424/472
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

A composition of matter is disclosed and claimed comprising an opioid antagonist and a high molecular weight poly(alkylene) or a poly(carboxymethylcellulose). A dosage form is disclosed and claimed comprising the composition of matter for displacing an opioid analgesic from the dosage form.

Claims

1. An osmotic dosage form comprising:

(a) a wall comprising a semipermeable composition, which wall surrounds;

(b) a bilayer core comprising;

(i) a first layer comprising 75 ng to 750 mg of an analgesic opioid;

(ii) a second push-displacement layer in bilayered contact with the first layer comprising 40 to 99 wt % of a poly(alkylene oxide) possessing a number-average molecular weight to 10,000,000, and 0.25 to 25 wt % of a hydroxyalkylcellulose possessing a number-average molecular weight to 75,000, and wherein the second layer is characterized by comprising 0.75 to 10 wt % of an antagonist selected from the group consisting of naltrexone, naloxone, nalmefene, nalide, nalmexone, nalorphine and nalbuphine; and

,

(c) an exit in the wall in contact with the first layer comprising the analgesic opioid for the push-displacement layer to push the first layer comprising the analgesic opioid through the exit from the dosage form.

2. The dosage form according to claim 1, wherein the antagonist is present as the pharmaceutically acceptable salt.

3. The dosage form according to claim 1, wherein the second layer comprises an osmagent.

4. The dosage form according to claim 1, wherein the analgesic opioid comprises a member selected from the group consisting of apomorphine, apocodeine, codeine, dihydrocodeine, dihydromorphine, hydrocodone, hydroxymethylmorphinan, hydromorphone, methylmorphine, morphine, normorphine, oxycodone, benzylmorphine and oxymorphone.

5. The dosage form according to claim 1, wherein the analgesic opioid comprises a member selected from the group consisting of alfentanil, fentanyl, lofentanil and sufentanil.

6. The dosage form according to claim 1, wherein the second layer comprises an antioxidant.

7. The dosage form according to claim 1, wherein the first layer comprises a member selected from the group consisting of allylprodine, alphaprodine, anileridine, bezitramide, buprenorphine, butorphanol, clonitazene, cyclorphan, cyprenorphine, desomorphine, dextromoramide, dezocine, diampromide, dimenoxadol, eptazocine, ethylmorphone, hydroxypethidine, levophenacylmorphan, levorphan, necomorphine, normethadone, pholcodine and profadol, and wherein the first layer composition is free of antagonist.

8. An osmotic dosage form comprising:

(a) a wall comprising a semipermeable composition, which wall surrounds;

(b) a bilayer core comprising;

(i) a first layer comprising 75 ng to 750 mg of an analgesic opioid;

(ii) a second push-displacement layer in contact with the first layer comprising 20 to 99 wt % of a poly(carboxymethylcellulose) comprising a number-average molecular weight to 2,500,000; and

0.25 to 25 wt % of a hydroxyalkylcellulose possessing a number-average molecular weight to 75,000, and wherein the second layer is characterized by comprising 0.75 to 10 wt % of an antagonist selected from the group consisting of naltrexone, naloxone, nalmefene, nalide, nalmexone, nalorphine and nalbuphine; and

,

(c) an exit in the wall in contact with the first layer for releasing the analgesic opioid by the push-displacement layer pushing the analgesic opioid through the exit from the dosage form.

9. The dosage form according to claim 8, wherein the antagonist is present as the pharmaceutically acceptable salt.

10. The dosage form according to claim 8, wherein the analgesic opioid comprises a member selected from the group consisting of apomorphine, apocodeine, codeine, dihydrocodeine, dihydromorphine, hydrocodone, hydroxymethylmorphan, hydromorphone, methylmorphine, morphine, normorphine, oxycodone, benzylmorphine and oxymorphone.

11. The dosage form according to claim 8, wherein the analgesic opioid comprises a member selected from the group consisting of alfentanil, fentanyl, lofentanil and sufentanil.

12. The dosage form according to claim 8, wherein the first layer is a composition comprising a member selected from the group consisting of allylprodine, alphaprodine, anileridine, bezitramide, buprenorphine, butorphanol, clonitazene, cyclorphan, cyprenorphine, desomorphine, dextromoramide, dezocine, diampromide, dimenoxadol, eptazocine, ethylmorphine, hydroxypethidine, levophenacylmorphan, levorphanol, necomorphine, normethadone, pholcodine and profadol, and wherein the first layer composition is free of antagonist and pressed as a tablet.

13. The dosage form according to claim 8, wherein the dosage form comprises a member selected from the group consisting of d-alpha tocopherol acetate, dl-alpha tocopherol, ascorbyl palmitate, ascorbic acid, butylated hydroxyanidate, butylated hydroxytoluene and propylgallate.

14. A composition comprising 10 ng to 275 mg of naloxone and 15 to 750 mg of a poly(alkylene oxide) comprising a molecular weight to 10,000,000.

15. The composition of matter according to claim 14, wherein the naloxone is replaced by a member selected from the group consisting of naltrexone, nalmefene, nalide, nalmexone, nalorphine and nalbuphine, and the composition is compressed into a tablet.

16. A composition comprising 10 ng to 275 mg of naloxone and 15 to 750 mg of a poly(alkylene oxide) comprising a molecular weight to 2,500,000.

17. The composition of matter according to claim 16, wherein the naloxone is replaced by a member selected from the group consisting of naltrexone, nalmefene, nalide, nalmexone, nalorphine and nalbuphine, and wherein the composition is compressed into a tablet.

18. A composition of matter comprising 10 ng to 275 mg of naloxone, 15 to 750 mg of a poly(alkylene oxide) comprising a molecular weight to 10,000,000, 5 to 350 mg of an osmagent, and 0.05 to 7.5 mg of an antioxidant.

19. A composition of matter comprising 10 ng to 275 mg of naloxone, 15 to 750 mg of a poly(carboxymethylcellulose) comprising a molecular weight to 2,500,000, 5 to 350 mg of an osmagent, and 0.05 to 7.5 mg of an antioxidant.