Effervescent Antimicrobial Composition for GI Tolerability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing antimicrobial compositions for oral administration cause significant gastrointestinal side effects and contribute to antibiotic resistance due to residual agents in the gastrointestinal tract, necessitating the development of formulations that minimize their presence and side effects.
Innovation Solution
A pharmaceutical composition combining a quinolone carboxylic acid derivative, such as delafloxacin meglumine, with an effervescent agent like sodium bicarbonate, sodium dihydrogen phosphate, and citric acid, which enhances gastrointestinal tolerability and reduces residual antimicrobial agent presence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If an antimicrobial agent is administered to achieve systemic concentrations above minimum inhibitory concentration, then therapeutic efficacy is improved, but gastrointestinal side effects worsen due to residual agent in the gastrointestinal tract
Solution Approach 1:
The patent changes the physical-chemical parameters of the antimicrobial agent by converting it from a traditional solid dosage form to an effervescent formulation. This involves changing the dissolution characteristics and release profile of the drug, allowing it to rapidly dissolve in gastrointestinal fluids and achieve systemic absorption more efficiently, thereby reducing residual amounts that cause side effects while maintaining therapeutic efficacy
Solution Approach 2:
The effervescent components (carbonate/bicarbonate and organic acid) act as intermediaries that facilitate the delivery of the antimicrobial agent. When the tablet contacts gastrointestinal fluids, these components react to produce carbon dioxide bubbles that enhance wetting and dissolution of the drug, improving bioavailability and reducing the amount of residual agent that causes gastrointestinal irritation
2Reliability
If an antimicrobial agent is administered to treat bacterial infections, then infection treatment is improved, but bacterial resistance worsens due to selective pressure on gastrointestinal flora
Solution Approach 1:
By changing the dissolution and absorption parameters through effervescent formulation, the drug achieves more complete and rapid absorption into the bloodstream. This reduces the concentration of residual antimicrobial agent in the gastrointestinal tract, thereby decreasing the selective pressure on gastrointestinal bacteria that leads to resistance development, while maintaining effective treatment of the target infection
Solution Approach 2:
The formulation effectively extracts or removes the harmful selective pressure effect from the gastrointestinal environment by improving systemic absorption. The effervescent mechanism ensures that less drug remains in the gastrointestinal tract to exert selective pressure on resident flora, thus taking out the resistance-inducing effect while preserving the therapeutic action against the pathogenic infection
3Ease of manufacture
If a traditional solid dosage form is used, then manufacturing simplicity is improved, but gastrointestinal tolerability worsens
Solution Approach 1:
The patent creates a composite tablet formulation that combines the antimicrobial agent with effervescent components (carbonate/bicarbonate and organic acid). This composite structure maintains the simplicity of a single-tablet dosage form while incorporating multiple functional elements that work together to improve gastrointestinal tolerability through enhanced dissolution and absorption, avoiding the need for complex multi-component delivery systems
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 composition improves gastrointestinal tolerability, reduces side effects like diarrhea and flatulence, and minimizes bacterial resistance by effectively delivering the antimicrobial agent while maintaining therapeutic efficacy.
Implementation Method 1
an effervescent agent, wherein said effervescent agent comprises a mixture of sodium bicarbonate, sodium dihydrogen phosphate, and citric acid
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to pharmaceutical compositions comprising a quinolone carboxylic acid derivative antimicrobial agent and an effervescent agent. These compositions have improved gastrointestinal tolerability and/or reduced potential to cause gastrointestinal side effects. These compositions are useful for oral administration, for treating, preventing, or reducing the risk of microbial infections.