Intranasal Naloxone Composition for Preservative-Free Stability

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Solution Overview

Problem

There is a need for storage-stable formulations that enable untrained individuals to quickly deliver a therapeutically effective dose of a rapid-acting opioid receptor antagonist, such as naloxone, to opioid overdose patients, as naloxone has a short half-life and requires repeated administration.

Innovation Solution

Development of pharmaceutical compositions comprising naloxone or its pharmaceutically acceptable salts, configured for intranasal delivery, which are free of preservatives and include polyols like glycerin, and are sterilized using techniques like autoclave sterilization, ensuring stability and efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If naloxone is formulated for intranasal delivery without preservatives, then ease of operation and safety for untrained individuals is improved, but storage stability and shelf life deteriorate

Engineering Contradiction:

Improveease of administrationVSAvoidstorage stability

Core Design Contradiction:

Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent modifies the physical and chemical parameters of the formulation by incorporating specific excipients (polyols like glycerin or propylene glycol, buffers, and stabilizers) to maintain stability without preservatives. The pH is adjusted to 3.0-5.0 and the formulation includes chelating agents like EDTA to prevent degradation, enabling preservative-free storage while maintaining efficacy.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite pharmaceutical formulation combining naloxone hydrochloride with multiple excipients including polyols, buffers, and stabilizers. This composite structure provides both the stability needed for storage and the safety/efficacy needed for administration by untrained individuals.

Inventive Principle:

Principle #40Composite materials

2Speed

If naloxone is administered intranasally, then speed of administration is improved, but manufacturing complexity increases

Engineering Contradiction:

Improvespeed of administrationVSAvoidmanufacturing complexity

Core Design Contradiction:

SpeedVSDevice complexity

Solution Approach 1:

The patent divides the formulation into discrete unit doses, each containing a specific amount of naloxone (e.g., 2mg, 4mg, or 8mg). This segmentation simplifies manufacturing by allowing standardized production of individual doses that can be easily packaged and administered, reducing overall device complexity while maintaining rapid administration.

Inventive Principle:

Principle #1Segmentation

3Ease of operation

If naloxone formulation is made preservative-free, then safety and ease of use by untrained individuals is improved, but reliability of consistent dosing deteriorates

Engineering Contradiction:

Improvesafety for untrained usersVSAvoiddosing consistency

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The formulation incorporates self-preserving mechanisms through the use of polyols (glycerin or propylene glycol) at concentrations of 1-10%, which provide inherent antimicrobial properties without requiring additional preservatives. The pH buffer system (citrate, phosphate, or acetate buffers) maintains stable conditions that prevent degradation and ensure consistent dosing throughout the shelf life.

Inventive Principle:

Principle #25Self-service

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The formulations provide a stable and effective means for untrained individuals to administer naloxone quickly and effectively, reversing opioid overdoses with minimal adverse effects.

Implementation Method 1

pharmaceutical compositions comprising an opioid receptor antagonist such as naloxone or a pharmaceutically acceptable salt thereof or a hydrate thereof and a polyol (e.g., a polyol having a molecular weight less than 300 Da, e.g., propylene glycol or glycerin)

Methodology Applied

Scientific EffectSolvation: Solvation

Implementation Method 2

polyol (e.g., a polyol having a molecular weight less than 300 Da, e.g., propylene glycol or glycerin)

Methodology Applied

Scientific EffectHydrogen bonding:

Implementation Method 3

sterilized using techniques like autoclave sterilization

Methodology Applied

Scientific EffectThermal sterilization: Heating

Data Source

PatentUS12514854B2Drug products for intranasal administration and uses thereof

Publication Date: 2026.01.06 SUMMIT BIOSCI

AI summary

Provided herein are methods of using drug products adapted for nasal delivery comprising a device and a pharmaceutical composition comprising an opioid receptor antagonist, wherein the claimed invention provides a method of treating an opioid overdose or symptom thereof in a patient in need thereof, comprising intranasally administering to the patient an aqueous pharmaceutical solution consisting of, or an aqueous pharmaceutical composition consisting essentially of: (i) naloxone hydrochloride in an amount of about 9% by weight based on the total weight of the aqueous pharmaceutical solution; (ii) glycerin in an amount of about 1.4% by weight based on the total weight of the aqueous pharmaceutical solution; (iii) a citrate buffer system adjusted by hydrochloric acid and/or sodium hydroxide; and (iv) United States Pharmacopeia (USP)—grade Purified Water; wherein the pH of the aqueous pharmaceutical solution is from about 3.5 to about 4.7; and wherein the hydrochloric acid and the sodium hydroxide may each be independently present in the aqueous pharmaceutical solution, as required, to achieve the pH from about 3.5 to about 4.7.