Intranasal naloxone compositions and methods of making and using same

• US 9,289,425 B2
• Filed: 10/14/2015
• Issued: 03/22/2016
• Est. Priority Date: 12/20/2013
• Status: Active Grant

• Current Assignee: Indivior UK Limited (Indivior Plc)
• Original Assignee: AntiOp, Inc.
• Inventors: Wyse, Joseph, DeHart, Michael Paul
• Primary Examiner(s): SHIAO, REI TSANG
• Application Number:
  US14/882,857
• Publication Number:
  US 20160038480A1
• Time in Patent Office: 160 Days
• Field of Search: 514/23
• US Class Current: 1/1
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 25/36 Opioid-abuse

Abstract

Disclosed herein are compositions containing an opioid antagonist such as naloxone and one or more pharmaceutically acceptable excipients. The compositions may be used for intranasal delivery of Naloxone for the treatment of, for example, opioid overdose in an individual in need thereof. Also disclosed are methods of making compositions containing Naloxone, and devices for nasal delivery of naloxone compositions.

Claims

1. A method of treating a known or suspected opioid overdose comprising the step of intranasally administering a composition comprising from about 5 mg/mL to about 50 mg/mL of an opioid antagonist naloxone;

from about 5 mM to about 50 mM citric acid;

from about 2 to about 20 mM disodium ethylene diamine tetraacetic acid (EDTA);

from about 0.1 to about 2 weight % benzyl alcohol; and

a carrier to an individual in need thereof,

wherein said composition is administered via the nasal membranes to said individual;

wherein said individual is administered a dose, per naris, of from about 0.1 to about 2 mg.

2. The method of claim 1, wherein said known or suspected opioid overdose is manifested by respiratory and/or central nervous system depression.

3. The method of claim 1, wherein said intranasal administration results in a T_max of about 5 to about 30 minutes.

4. The method of claim 1, wherein said method utilizes a device having a property selected from needle-free, ready-to-use, disposable, or a combination thereof.

5. The method of claim 1, wherein said administration step comprises intranasal administration of a single spray per naris, wherein said spray may be repeated as necessary.

6. The method of claim 1, wherein administration of said composition intranasally results in a parameter selected from a T_max of about 0.1 hours to about 0.5 hours in a subject;

a peak plasma concentration of from about 1.0 to about 4.0 ng/mL at a time period of from about 5 to about 30 minutes after administration; and

combinations thereof.

7. The method of claim 1, wherein said composition comprises

a) about 10 mg/mL naloxone HCl dihydrate;

b) about 25 mM citric acid;

c) about 10 mM EDTA;

d) about 0.5 weight % benzyl alcohol; and

e) a pharmaceutically acceptable carrier;

wherein intransal administration of about 200 μ

L of said composition achieves one or more parameters selected from a plasma concentration of about 1 ng/mL within about 5 to 15 minutes after intranasal administration;

a T_max of about 0.1 hours to about 0.5 hours, or about 0.3 hours;

an AUC_0-inf of from about 2.5 to about 4.5 ng−

hr/mL, or about 2.5 to about 2.7 ng−

hr/mL, or about 2.6 ng−

hr/mL; and

a Cmax of from about 1 to about 3 or about 1.5 to about 2.5 or about 1.8 ng/mL.

8. The method of claim 1, wherein said composition comprises

a) about 7 mg/mL to about 11 mg/mL naloxone;

b) about 20 mM to about 30 mM citric acid;

c) about 5 mM to about 15 mM ethylenediaminetetraacetic acid; and

d) about 0.2% to about 1.0 weight % benzyl alcohol;

wherein the nasal spray has a pH of about 4.25±

0.1.

9. The method of claim 1, wherein said composition comprises from about 5 mg/mL to about 50 mg/mL of naloxone;

a) from about 5 mM to about 50 mM citric acid;

b) from about 2 to about 20 mM disodium ethylene diamine tetraacetic acid (EDTA);

c) from about 0.1 to about 2 weight % benzyl alcohol; and

d) a carrier;

wherein said composition has a pH of about 4; and

wherein said composition has an osmolality of from about 300 to about 500 mOsm.

10. The method of claim 1, wherein said composition comprises naloxone hydrochloride dihydrate.