High concentration formulations of opioids and opioid derivatives

• US 20040102476A1
• Filed: 11/25/2002
• Published: 05/27/2004
• Est. Priority Date: 11/25/2002
• Status: Abandoned Application

• Current Assignee: DURECT Corporation
• Original Assignee: DURECT Corporation
• Inventors: Tamraz, Wilma, Lee, Min, Chan, Tai Wah
• Application Number:
  US10/305,252
• Publication Number:
  US 20040102476A1
• Time in Patent Office: Days
• US Class Current: 514/317
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides opioid formulations suitable for long-term delivery to a subject. The formulation of the invention comprises an opioid or opioid derivative (e.g., morphine, hydromorphone, fentanyl or a fentanyl congener), and an aqueous solvent comprising a low molecular weight carboxylic acid (e.g., C_2-4, C_2-7). The invention thus provides for formulations comprising morphine, hydromorphone, fentanyl or fentanyl congeners in concentrations significantly in excess of conventional aqueous formulations, e.g., on the order about 2-fold to about 10,000-fold greater than conventional formulations, e.g., currently commercially available formulations.

Claims

1. A pharmaceutical formulation comprising:

a low molecular weight carboxylic acid or salt thereof; and

a drug selected from the group consisting of fentanyl or a fentanyl congener;

wherein the drug is present in the formulation at a concentration of at least about 5 mg/mL.

2. The pharmaceutical formulation of claim 1, where the carboxylic acid is acetic acid, lactic acid, or a salt thereof.

3. The pharmaceutical formulation of claim 1, where the drug is sufentanil.

4. The pharmaceutical formulation of claim 3, where the carboxylic acid is acetic acid, lactic acid, or a salt thereof.

5. The pharmaceutical formulation of claim 1, where the drug is fentanyl.

6. The pharmaceutical formulation of claim 1, wherein the drug is present in the formulation at a concentration of at least about 50 mg/mL.

7. The pharmaceutical formulation of claim 1, wherein the drug is present in the formulation at a concentration of at least about 100 mg/mL.

8. The pharmaceutical formulation of claim 1, wherein the drug is present in the formulation at a concentration of at least about 200 mg/mL.

9. The pharmaceutical formulation of claim 1, wherein the drug is present in the formulation at a concentration of at least about 500 mg/mL.

25. A dosage form adapted for sustained delivery of a drug to a subject, the dosage from comprising the pharmaceutical formulation according to claim 1.

26. A dosage form adapted for sustained delivery of a drug to a subject, the dosage from comprising the pharmaceutical formulation according to claim 1.

29. A method of treating pain in a subject, comprising administering the pharmaceutical formulation according to claim 1 to the subject in an amount effective to alleviate pain in the subject.

10. A pharmaceutical formulation comprising:

a low molecular weight carboxylic acid or salt thereof; and

a drug selected from the group consisting of fentanyl or a fentanyl congener;

wherein the molar ratio of carboxylic acid or carboxylic acid salt to drug in the formulation is greater than about 0.5.

11. The pharmaceutical formulation of claim 10, where the carboxylic acid is acetic acid, lactic acid, or a salt thereof.

12. The pharmaceutical formulation of claim 10, where the drug is sufentanil.

13. The pharmaceutical formulation of claim 12, where the carboxylic acid is acetic acid, lactic acid, or a salt thereof.

14. The pharmaceutical formulation of claim 10, where the drug is fentanyl.

15. The pharmaceutical formulation of claim 10, wherein the molar ratio of carboxylic acid or carboxylic acid salt to drug in the formulation is greater than about 1.

16. The pharmaceutical formulation of claim 10, wherein the molar ratio of carboxylic acid or carboxylic acid salt to drug in the formulation is greater than about 2.

17. The pharmaceutical formulation of claim 10, wherein the molar ratio of carboxylic acid or carboxylic acid salt to drug in the formulation is greater than about 2.5.

27. A dosage form adapted for sustained delivery of a drug to a subject, the dosage from comprising the pharmaceutical formulation according to claim 10.

30. A method of treating pain in a subject, comprising administering the pharmaceutical formulation according to claim 10 to the subject in an amount effective to alleviate pain in the subject.

18. A pharmaceutical formulation comprising:

a low molecular weight carboxylic acid or salt thereof; and

an opioid or opioid derivative;

wherein the opioid or opioid derivative is presenting the formulation at a concentration of at least about 20 mg/mL and an aqueous carrier comprising a carboxylic acid, or a salt thereof.

19. The pharmaceutical formulation of claim 18, where the carboxylic acid is acetic acid, lactic acid, or a salt thereof.

20. The pharmaceutical formulation of claim 18, wherein the opioid or opioid derivative is selected from the group consisting of morphine, hydromorphone, fentanyl, and sufentanil.

21. The pharmaceutical formulation of claim 18, wherein the opioid or opioid derivative is hydromorphone.

22. The pharmaceutical formulation of claim 21, where the carboxylic acid is acetic acid, lactic acid, or a salt thereof.

23. The pharmaceutical formulation of claim 18, wherein the drug is present in the formulation at a concentration of at least about 100 mg/mL.

24. The pharmaceutical formulation of claim 18, wherein the drug is present in the formulation at a concentration of at least about 500 mg/mL.

28. A dosage form adapted for sustained delivery of a drug to a subject, the dosage from comprising the pharmaceutical formulation according to claim 18.

31. A method of treating pain in a subject, comprising administering the pharmaceutical formulation according to claim 18 to the subject in an amount effective to alleviate pain in the subject.