NASAL DRUG PRODUCTS AND METHODS OF THEIR USE
Drug products adapted for nasal delivery, comprising a pre-primed device filled with a pharmaceutical composition comprising an opioid receptor antagonist, are provided. Methods of treating opioid overdose or its symptoms with the inventive drug products are also provided.
1 . A prefilled nasal delivery device comprising:
a reservoir containing a pharmaceutical composition comprising naloxone hydrochloride, an amount of water sufficient to achieve a therapeutically effective amount of about 8 mg naloxone hydrochloride per 100 μL, an amount of hydrochloric acid sufficient to achieve a pH of 3.5-5.5, and propylene glycol, and;
wherein the device is configured to deliver the therapeutically effective amount of about 8 mg naloxone hydrochloride or an equivalent thereof in a single use device to a patient suffering from or suspected to be suffering from opioid overdose, without the need for a caregiver to prime the device.
2 . The prefilled nasal delivery device of claim 1 , wherein the pharmaceutical composition further comprises disodium edetate.
3 . The prefilled nasal delivery device of claim 1 , wherein the pharmaceutical composition further comprises an alcohol.
4 . The prefilled nasal delivery device of claim 1 , wherein naloxone hydrochloride is the only pharmaceutically active compound in the pharmaceutical composition.
5 . The prefilled nasal delivery device of claim 1 , wherein the pharmaceutical composition is storage stable.
6 . The prefilled nasal delivery device of claim 1 , wherein the patient is a human.
7 . The prefilled nasal delivery device of claim 1 , wherein the pharmaceutical composition provides a maximum observed plasma concentration of naloxone after administration (C max ) of about 9.52 ng/ml to about 10.9 ng/ml after delivery to the patient.
8 . The prefilled nasal delivery device of claim 1 , wherein the pharmaceutical composition provides a C max of about 10.3 ng/ml of naloxone after delivery to the patient.
9 . The prefilled nasal delivery device of claim 1 , wherein a plasma concentration versus time curve of naloxone in the patient has a T max of 0.33 hours or less after delivery of the pharmaceutical composition to the patient.
10 . The prefilled nasal delivery device of claim 1 , wherein the plasma concentration versus time curve of naloxone in the patient has a T max of less than 20 minutes after delivery of the pharmaceutical composition to the patient.
11 . The prefilled nasal delivery device of claim 1 , wherein the plasma concentration versus time curve of naloxone in the patient has a T max of less than 19 minutes after delivery of the pharmaceutical composition to the patient.
12 . The prefilled nasal delivery device of claim 1 , wherein the plasma concentration versus time curve of naloxone in the patient has a T max of less than 18.5 minutes after delivery of the pharmaceutical composition to the patient.
13 . The prefilled nasal delivery device of claim 1 , wherein the pharmaceutical composition has an area under the drug plasma concentration-time curve AUC 0-∞ of about 15.0 ng*mL/h to about 16.9 ng*mL/h of naloxone after delivery of the pharmaceutical composition to the patient.