Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Intranasal Pharmaceutical Dosage Forms Comprising Naloxone

a technology of naloxone and intranasal, which is applied in the direction of aerosol delivery, anti-noxious agents, inorganic non-active ingredients, etc., can solve the problems of low bioavailability, unsuitable for such purposes, and addicts' deaths, and achieves high bioavailability of naloxone, fast onset of action, and long duration of action

Inactive Publication Date: 2015-01-15
EURO-CELTIQUE SA
View PDF1 Cites 18 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent is about a new pharmaceutical form of naloxone that has high bioavailability and a fast onset of action. The formulation allows for a long period of action and is designed to quickly reach the active site in the body. This makes it easier to treat opioid addiction and other medical conditions.

Problems solved by technology

Such overdosing incidents can lead to the death of the addict (so called “fatal overdosing”).
Thus, non-fatal overdosing represents a considerable number of events among drug addicts, especially in drug addicts who abuse the drug parenterally, i.e. by injection, requiring an adequate instant treatment by emergency health care personnel.
Due to a high first pass metabolism, oral dosage forms comprising naloxone display a low bioavailability and thus seem to be not suitable for such purposes.
Secondly, depending on the constitution of the addict and the period of intravenous drug abuse, it can be particularly difficult to find access into a vein of the addict's body for administering naloxone intravenously.
Clearly, there is a risk of exposure to blood borne pathogens for the medical personnel or the trained carer since a large population of drug addicts suffers from blood borne pathogen induced diseases such as HIV, hepatitis B and C, and the like since accidental needlestick is a serious safety concern.
Furthermore, due to the relatively short elimination half life of naloxone administered intravenously, there is the need to re-administer naloxone, in some cases even several times, via this route.
However, their outcome is rather controversial.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Intranasal Pharmaceutical Dosage Forms Comprising Naloxone
  • Intranasal Pharmaceutical Dosage Forms Comprising Naloxone
  • Intranasal Pharmaceutical Dosage Forms Comprising Naloxone

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0178]In the following, the results of a single-center, open-label, randomized investigation in healthy volunteers to determine the intranasal and sublingual bioavailabilities of naloxone in a four-way crossover study are set out.

Summary of the Study

[0179]Objectives: To assess the absolute bioavailability of 8 mg and 16 mg intranasally and 16 mg sublingually administered naloxone compared with 1 mg of intravenously administered naloxone to healthy subjects.

Methodology: A single-center, open-label, randomized, 4-way crossover study using 8 mg and 16 mg intranasally, 16 mg naloxone sublingually, and 1 mg intravenous naloxone. A 4-sequence Williams design was used.

Number of Subjects: Planned: 12 subjects; full analysis for PK metrics: 12 subjects; Safety population: 12 subjects; Completed: 10 subjects; Discontinued: 2 subjects [due to their own choice].

Indication and Criteria for Inclusion: Subjects were males and / or females aged ≧18 and ≦55 years who were in good health as determined ...

example 2

[0227]Based on the data gained in Example 1, the following predictions of amounts of naloxone administered intravenously or intranasally were carried out.

[0228]A typical starting point for an intravenous administration of naloxone is in the range of about 0.4 mg (IV). Based on the AUC-values for 1 mg IV naloxone, 8 mg IN naloxone and 16 mg IN of example 1, it can be estimated that the range of dose-proportionality to 1 mg IV is in the range of 3 mg to 4 mg for IN naloxone. For 0.4 mg IV naloxone, this results in typical starting amounts for naloxone administered intranasally ranging from 1.2 mg to 1.6 mg.

[0229]Based on the original data of the study of example 1 on either 8 mg naloxone or 16 mg naloxone administered intranasally (IN) and of 1 mg naloxone administered intravenously (IV), plasma concentrations were predicted for the following amounts: 0.4 mg naloxone IV, 1.2 mg naloxone IN and 1.6 mg naloxone IN.

[0230]Using a first method (Excel), the Cmax and AUCt-values based on the...

example 3

[0239]As evident particularly from FIGS. 4, 6, 7 and 8, the plasma concentration curve predicted for an amount of 0.4 mg naloxone IV displays two peaks, wherein the first peak after a few minutes is followed by a second peak corresponding to the Cmax-peak.

[0240]Due to this rather unusual IV profile, it was decided to exclude one outlying subject who was apparently responsible for the “double peak IV profile” when predicting the plasma concentration curve for an amount of 0.4 mg naloxone administered intravenously. The calculations using Excel and WinNonlin for the 1.2 mg naloxone IN and 1.6 mg naloxone IN correspond to the data as shown in Example 2.

[0241]Using Excel, the Cmax and AUCt-values based on the 1 mg naloxone IV data excluding the outlying subject were calculated by performing non-compartmental analysis on the mean profiles which had been scaled to the dose of 0.4 mg IV with the following results (depicted again with the IN-values based on the 8 mg IN data):

Cmax (pg / ml)AUC...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
volumeaaaaaaaaaa
volumeaaaaaaaaaa
volumeaaaaaaaaaa
Login to View More

Abstract

The present invention relates to an intranasal pharmaceutical dosage form comprising a dosing unit comprising naloxone or a pharmaceutically acceptable salt thereof in an amount of equivalent to ≧0.5 mg naloxone HCl dissolved in an application fluid of a volume of ≦250 μl. Furthermore, the present invention relates to such an intranasal pharmaceutical dosage form for use in the treatment of opioid overdosing and / or at least one symptom thereof.

Description

FIELD OF THE INVENTION[0001]The present invention relates to an intranasal pharmaceutical dosage form comprising a dosing unit comprising naloxone or a pharmaceutically acceptable salt thereof in an amount of equivalent to ≧0.5 mg naloxone HCl, preferably an amount of equivalent to between about 0.65 mg naloxone HCl and about 0.8 mg naloxone HCl or between about 1.3 mg naloxone HCl and about 1.6 mg naloxone HCl, dissolved in an application fluid of a volume of ≦250 μl. Preferably, the dosage form is for use in the treatment of opioid overdosing and / or at least one symptom thereof.BACKGROUND OF THE INVENTION[0002]The abuse of opioids, in particular the intravenous injection of opioids such as heroin by drug addicts is quite often associated with overdosing of the drug which can be due to a loss of opioid tolerance (e.g. when abusers are imprisoned or following substitution / detoxification therapy), wrong estimation of the amount of the drug consumed, a more concentrated form of the dr...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/00A61K31/485
CPCA61K31/485A61K9/0043A61K9/08A61K9/12A61P11/00A61P25/00A61P25/04A61P25/36A61P39/02A61P43/00A61K47/02A61K9/0019
Inventor STRANG, JOHNOKSCHE, ALEXANDERHARRIS, STEPHENSMITH, KEVINMOTTIER, LUCIE HELENE JEANNE
Owner EURO-CELTIQUE SA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com