Abusable substance dosage form having reduced abuse potential

• US 5,236,714 A
• Filed: 11/01/1988
• Issued: 08/17/1993
• Est. Priority Date: 11/01/1988
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Goetz, Victor, Lee, Eun S.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Horna, Leon R.
• Application Number:
  US07/265,738
• Time in Patent Office: 1,750 Days
• Field of Search: 424/448, 424/449
• US Class Current: 424/449
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: B09B 2101/68 Transdermal patches
• CPC Class Codes: B09B 3/0075 Disposal of medical waste casings for used articles, e.g. sharps A61B50/362; sterilisation of refuse A61L11/00; disposal of used needles or syringes A61M5/3205; disintegrating medical waste B02C19/0075

Abstract

Compositions and dosage forms for administering abusable substances are disclosed which have a reduced potential for abuse without diminishing the therapeutic or beneficial effects of the abusable substance. Topical compositions for application to the skin or mucosa contain the abusable substance in a form which is permeable to the skin or mucosa to which it is to be applied and an antagonist for the abusable substance is present in the composition in an abuse negating amount and in a form that is impermeable to the skin or mucosa to which the composition is to be applied. Controlled release dosage forms which release the abusable substance from a drug reservoir composition confined behind a release rate controlling barrier have the abusable substance and its antagonist in the drug reservoir. The abusable substance is present in a form that is releasable from the dosage form and the antagonist is present in an abuse negating amount in a form that is not releasable from the dosage form. Thus the compositions and dosage forms of this invention permit the therapeutic use, at substantially full potency, of an abusable substance when use as prescribed but reduce the abuse potential of the compositions and dosage forms by other routes of administration. Preferred embodiments of the invention utilize fentanyl as the abusable substance and naltrexone as the antagonist in a transdermal dosage form.

Claims

1. A method for administering an abusable substance to the skin or mucosa to produce a predetermined beneficial effect which comprises:

a) contacting the skin or mucose with a composition comprising a mixture of;

i) an amount of an abusable substance in a form that is permeable to the skin or mucosa to which it is intended to be applied; and

ii) an abuse negating amount of at least one antagonist for said abusable substance in a form that is impermeable to the skin or mucosa to which it is to be applied; and

b) maintaining said composition on the skin or mucosa for a period of time at least sufficient for the abusable substance to produce the beneficial effect.

14. The method of claim 1 wherein said antagonist is selected from the group consisting of naloxone, naltrexone, nalbuphine, nalorphine and levallorphan.

2. A method for administering an abusable substance to the body from a dosage form having a reduced potential for abuse comprising:

a) placing a dosage form containing an amount of an abusable substance and an abuse negating amount of at least one antagonist for said abusable substance in abusable substance delivering relationship to the body;

b) delivering said abusable substance to the body from said dosage form; and

c) retaining said antagonist within said dosage form.

17. The method of claim 2 wherein said antagonist is selected from the group consisting of naloxone, naltrexone, nalbuphine, nalorphine and levallorphan.

3. A composition of matter for the administration of an abusable substance by application of the composition to the skin or mucosa, said composition having a reduced potential for abuse and comprising a mixture of:

a) an amount of an abusable substance in a form that is permeable to the skin or mucosa to which it is intended to be applied; and

b) an abuse negating amount of at least one antagonist for said abusable substance in a form that is impermeable to the skin or mucosa to which it is to be applied.

4. The composition of claim 3 further comprising a pharmaceutically acceptable carrier within which said abusable substance and said antagonist are dispersed.

5. The composition of claim 3 wherein said antagonist is selected from the group of impermeable forms of naloxone, naltrexone, nalbuphine and levallorphan.

6. The composition of claim 3 wherein said antagonist is naltrexone.

7. A dosage form for administering an abusable substance to the body, said dosage form having a reduced potential for abuse and comprising, in combination:

a) abusable substance releasing means through which said abusable substance is released to the body; and

b) a drug reservoir separated from the body by said releasing means, said reservoir comprising a mixture of said abusable substance and an abuse negating amount of at least one antagonist for said abusable substance;

i) said abusable substance being present in said reservoir in a form that is releasable to the body through said releasing means; and

ii) said antagonist being present in said reservoir in a form that is not releasable through said releasing means.

8. The dosage form of claim 7 wherein said releasing means comprises a semipermeable material permeable to water and impermeable to said abusable substance and said antagonist and said drug reservoir comprises a water soluble form of said abusable substance and a water insoluble form of said antagonist and said semipermeable material is provided with outlet means for a solution of said abusable substance.

9. The dosage form of claim 7 wherein said releasing means is permeable to said abusable substance and impermeable to said antagonist.

21. The dosage form of claim 7 wherein said antagonist is selected from the group consisting of naloxone, naltrexone, nalbuphine, nalorphine and levallorphan.

10. A dosage form for the administration of an abusable substance through the skin or mucosa, said dosage form having a reduced potential for abuse and comprising:

a) abusable substance releasing means through which said abusable substance is released to the skin or mucosa;

b) a drug reservoir separated from the skin or mucosa by said releasing means, said reservoir comprising a mixture of said abusable substance and an abuse negating amount of at least one antagonist for said abusable substance;

i) said abusable substance being present in said reservoir in a form that is releasable to the skin through said releasing means; and

ii) said antagonist being present in said reservoir in a form that is not releasable through said releasing means; and

c) means for maintaining said reservoir in abusable substance releasing relationship to the skin or mucosa.

11. The dosage form of claim 10 wherein said releasing means comprises a semipermeable material permeable to water and impermeable to said abusable substance and said antagonist and said drug reservoir comprises a water soluble form of said abusable substance and a water insoluble form of said antagonist and said semipermeable material is provided with outlet means for a solution of said abusable substance.

12. The dosage form of claim 10 wherein said releasing means is permeable to said abusable substance and impermeable to said antagonist.

24. The dosage form of claim 10 wherein said antagonist is selected from the group consisting of naloxone, naltrexone, nalbuphine, nalorphine and levallorphan.

13. A method for administering an abusable substance selected from the group consisting of fentanyl, sufentanil, carfentanil, lofentanil, alfentanil, hydromorphone, oxycodone, propoxyphene, pentazocine, methadone, tilidine, butorphanol, buprenorphine, levorphanol, codeine, oxymorphone, meperidine, dihydrocodeinone and cocaine to the skin or mucosa to produce a predetermined beneficial effect which comprises:

a) contacting the skin or mucosa with a composition comprising a mixture of;

(i) an amount of said abusable substance in a form that is permeable to the skin or mucosa to which is intended to be applied; and

(ii) an abuse negating amount of at least one antagonist for said abusable substance in a form that is impermeable to the skin or mucosa to which it is to be applied; and

b) maintaining said composition on the skin or mucosa for a period of time at least sufficient to produce the beneficial effect.

15. The method of claim 13 wherein said antagonist is selected from the group consisting of naloxone, naltrexone, nalbuphine, nalorphine and levallorphan.

16. A method for administering an abusable substance selected from the group consisting of fentanyl, sufentanil, carfentanil, lofentanil, alfentanil, hydromorphone, exycodone, propoxyphene, pentazocine, methadone, tilidine, butorphanol, buprenorphine, levorphanol, codeine, oxymorphone, meperidine, dihydrocodeinone and cocaine to the body from a dosage form having a reduced potential for abuse comprising:

a) placing a dosage form containing an amount of an abusable substance and an abuse negating amount of at least one antagonist for said abusable substance in abusable substance delivering relationship to the body;

b) delivering said abusable substance to the body from said dosage form; and

c) retaining said antagonist within said dosage form.

18. The method of claim 16 wherein said antagonist is selected from the group consisting of naloxone, naltrexone, nalbuphine, nalorphine and levallorphan.

19. A composition of matter for the administration of an abusable substance selected from the group consisting of fentanyl, sufentanil, carfentanil, lofentanil, alfentanil, hydromorphone, oxycodone, propoxyphene, pentazocine, methadone, tilidine, butorphanol, buprenorphine, levorphanol, codeine, oxymorphone, meperidine, dihydrocodeinone and cocaine by application of the composition to the skin or mucosa, said composition having a reduced potential for abuse and comprising a mixture of:

a) an amount of an abusable substance in a form that is permeable to the skin or mucosa to which it is intended to be applied; and

b) an abuse negating amount of at least one antagonist for said abusable substance in a form that is impermeable to the skin or mucosa to which it is applied.

29. The composition of claim 19 wherein said antagonist is selected from the group consisting of naloxone, naltrexone, nalbuphine, nalorphine and levallorphan.

20. A dosage form for administering an abusable substance selected from the group consisting of fentanyl, sufentanil, carfentanil, lofentanil, alfentanil, hydromorphone, oxycodone, propoxyphene, pentazocine, methadone, tilidine, butorphanol, buprenorphine, levorphanol, codeine, oxymorphone, meperidine, dihydrocodeinone and cocaine to the body, said dosage form having a reduced potential for abuse and comprising, in combination:

a) abusable substance releasing means through which said abusable substance is release to body;

b) reservoir means separated from the body by said releasing means, said reservoir means comprising a mixture of said abusable substance and an abuse negating amount of at least one antagonist for said abusable substance;

(i) said abusable substance being present in said reservoir means in a form that is releasable to the body through said releasing means; and

(ii) said antagonist being present in said reservoir means in a form that is not releasable through said releasing means.

22. The dosage form of claim 20 wherein said antagonist is selected from the group consisting of naloxone, naltrexone, nalbuphine, nalorphine and levallorphan.

23. A dosage form for the administration of an abusable substance selected from the group consisting of fentanyl, sufentanil, carfentanil, lofentanil, alfentanil, hydromorphone, oxycodone, propoxyphene, pentazocine, methadone, tilidine, butorphanol, buprenorphine, levorphanol, codeine, oxymorphone, meperidine, dihydrocodeinone and cocaine through the skin or mucosa, said dosage form having a reduced potential for abuse and comprising:

a) abusable substance releasing means through which said abusable substance is released to the skin or mucosa;

b) reservoir means separated from the skin or mucosa by said releasing means, said reservoir means comprising a mixture of said abusable substance and an abuse negating amount of at least one antagonist for said abusable substance;

(i) said abusable substance being present in said reservoir means in a form that is releasable to the skin through said releasing means;

(ii) said antagonist being present in said reservoir in a form that is not releasable through said releasing means; and

c) means for maintaining said reservoir in abusable substance releasing relationship to the skin or mucosa.

25. The dosage form of claim 23 wherein said antagonist is selected from the group consisting of naloxone, naltrexone, nalbuphine, nalorphine and levallorphan.

26. A dosage form for the administration of fentanyl through the skin or mucosa, said dosage form having a reduced potential for abuse, comprising, in combination:

a) fentanyl releasing means through which fentanyl is released to the skin or mucosa;

b) reservoir means separated from the skin or mucosa by said releasing means, said reservoir comprising a mixture of fentanyl and an abuse negating amount of at least one antagonist for fentanyl;

(i) fentanyl being present in said reservoir in a form that is releasable to the skin or mucosa through said releasing means; and

(ii) antagonist being present in said reservoir in a form that is not releasable through said releasing means; and

c) means for maintaining said reservoir in abusable substance releasing relationship to the skin or mucosa.

27. The dosage form of claim 26 wherein said antagonist is selected from the group consisting of naloxone and naltrexone.

28. The dosage form of claim 27 wherein the releasing means comprises an ethylene vinyl acetate copolymer.