Mucosal 2-DG Dispenser With Acidic pH for Mucus Penetration
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Solution Overview
Problem
Existing formulations of 2-deoxy-glucose (2-DG) and its analogues for mucosal administration suffer from reduced bioavailability due to interaction with free amines in mucus, particularly in thick mucus conditions, leading to ineffective delivery and efficacy.
Innovation Solution
Formulating the pharmaceutical composition with a pH lower than 7.4, preferably between 3.0 and 7.0, and incorporating a buffering agent such as citrate, phosphate, or acetate to maintain this acidic pH, thereby reducing imine formation and enhancing mucus penetration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If 2-DG is administered mucosally in conventional formulations, then it interacts with free amines in mucus to form imines, but this reduces bioavailability and efficacy
Solution Approach 1:
The patent changes the pH parameter of the pharmaceutical composition to be lower than 7.4 (preferably 6.8-7.2), which suppresses the formation of imines between 2-DG and free amines in mucus, thereby improving bioavailability and reducing harmful interactions
Solution Approach 2:
The patent introduces a buffering agent as an intermediary substance that maintains the pH of the composition below 7.4, preventing direct harmful interaction between 2-DG and mucus amines while ensuring stable drug delivery
2Reliability
If the pH is reduced to prevent imine formation, then bioavailability increases, but formulation stability and safety must be maintained
Solution Approach 1:
The patent optimizes the pH parameter to a specific range (6.8-7.2) that balances multiple requirements: low enough to suppress imine formation and improve bioavailability, but high enough to maintain formulation stability and safety for mucosal administration
Solution Approach 2:
The buffering agent acts as a mediator that stabilizes the pH within the optimal range, preventing both excessive acidity that could harm mucosal tissues and insufficient acidity that would allow imine formation, thus ensuring formulation stability
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 acidic pH formulation significantly increases the bioavailability of 2-DG and its analogues, improving their efficacy in treating respiratory infections by enhancing penetration through mucosal barriers.
Implementation Method 1
the 2-DG and analogues interacted with free amines in the mucus, leading to the formation of Schiff's bases (imines)
Implementation Method 2
reducing the pH of the formulation improved mucus penetration, thereby increasing bioavailability
Data Source
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AI summary
Disclosed is a pharmaceutical dispenser for mucosal administration, preferably intranasal or inhalatory administration, containing a pharmaceutical composition. The pharmaceutical composition comprises an active pharmaceutical ingredient (API) selected from the group consisting of 2-deoxy-glucose (2-DG) and analogues thereof, or a pharmaceutically acceptable salt of the API. The pH of the pharmaceutical composition is lower than 7.4, optionally upon reconstitution in water. Also disclosed is a method for mucosally administering this pharmaceutical composition, preferably for preventing or treating an infection.