Pharmaceutical Compositions Comprising an Opioid Receptor Antagonist and Methods of Using Same

• US 20070212307A1
• Filed: 02/12/2007
• Published: 09/13/2007
• Est. Priority Date: 02/10/2006
• Status: Abandoned Application

• Current Assignee: Intranasal Therapeutics, Inc. (SAWAI GROUP HOLDINGS Co., Ltd.), University Of Kentucky Research Foundation (University of Kentucky)
• Original Assignee: University Of Kentucky Research Foundation (University of Kentucky)
• Inventors: Wermeling, Daniel, Cohen, Edwin, Rudy, Anita
• Application Number:
  US11/673,874
• Publication Number:
  US 20070212307A1
• Time in Patent Office: Days
• US Class Current: 424/45
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 25/32 Alcohol-abuse

Abstract

The present invention features compositions for intranasal administration comprising an opioid receptor antagonist. The invention also features methods of using such compositions in the treatment of various diseases and disorders, such as the treatment of alcoholism. In certain embodiments, the opioid receptor antagonist is naltrexone or a pharmaceutically acceptable salt thereof.

Claims

1. An intranasally deliverable pharmaceutical composition, comprising an opioid receptor antagonist or salt thereof and a liquid carrier, said opioid receptor antagonist or salt thereof having an absolute bioavailability of greater than about 30% when said pharmaceutical composition is administered to the nasal cavity of a human.

2. The pharmaceutical composition of claim 1, wherein the opioid receptor antagonist is naltrexone or salt thereof.

3. The pharmaceutical composition of claim 2, wherein the naltrexone or salt thereof is present in dissolved or solubilized form in the liquid carrier at a concentration of about 10 mg/mL to about 100 mg/mL.

4. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition further comprises at least one water miscible solvent.

5. The pharmaceutical composition of claim 4, wherein the water miscible solvent comprises propylene glycol, alcohol, glycerol, isopropyl alcohol, polyethylene glycol, or mixtures thereof.

6. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition further comprises a cellulose ether.

7. The pharmaceutical composition of claim 6, wherein the cellulose ether is hydroxypropyl methylcellulose.

8. The pharmaceutical composition of claim 1, wherein said opioid receptor antagonist or salt thereof has an absolute bioavailability of greater than about 50% when said pharmaceutical composition is administered to the nasal cavity of a human.

9. A method of treating or preventing alcoholism in a human, comprising administering intranasally to a human in need thereof a therapeutically effective amount of a pharmaceutical composition comprising an opioid receptor antagonist or a salt thereof and a liquid carrier, wherein said opioid receptor antagonist or salt thereof has an absolute bioavailability of greater than about 30% when said pharmaceutical composition is administered to the nasal cavity of a human.

10. The method of claim 9, wherein the opioid receptor antagonist is naltrexone or salt thereof.

11. The method of claim 10, wherein the naltrexone or salt thereof is present in dissolved or solubilized form in the liquid carrier at a concentration of about 10 mg/mL to about 100 mg/mL.

12. The method of claim 9, wherein the pharmaceutical composition further comprises at least one water miscible solvent.

13. The method of claim 12, wherein the water miscible solvent comprises propylene glycol, alcohol, glycerol, isopropyl alcohol, polyethylene glycol, or mixtures thereof.

14. The method of claim 9, wherein the pharmaceutical composition further comprises a cellulose ether.

15. The method of claim 14, wherein the cellulose ether is hydroxypropyl methylcellulose.

16. The method of claim 9, wherein the pharmaceutical composition has a pH in range of about 3.0 to about 6.5.

17. The method of claim 9, wherein said opioid receptor antagonist or salt thereof has an absolute bioavailability of greater than about 50% when said pharmaceutical composition is administered to the nasal cavity of a human.

18. The method of claim 9, wherein a single intranasal administration of said pharmaceutical composition is sufficient to deliver a dose in the range of about 2 mg to about 8 mg of said opioid receptor antagonist to the nasal cavity of said human.

19. The method of claim 10, wherein upon intranasal administration of said composition to a human subject, the subject exhibits one or more of:

a T_max naltrexone plasma concentration of less than about 0.75 hr;

a C_max naltrexone plasma concentration of at least about 2 ng/mL; and

/or an AUC naltrexone plasma concentration of at least about 5 ng*hr/mL.

20. A method of treating acute alcohol craving in a human, comprising administering intranasally to a human in need thereof a therapeutically effective amount of a pharmaceutical composition comprising an opioid receptor antagonist or a salt thereof and a liquid carrier, wherein at least a portion of the opioid receptor antagonist or salt thereof is present in dissolved or solubilized form in the liquid carrier.