Finafloxacin Solubility via Tris Buffering

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Solution Overview

Problem

Finafloxacin's poor solubility and instability in physiological solvents hinder its effective formulation as a stable, high-concentration parenteral composition for treating bacterial infections, particularly in intensive care patients where rapid drug delivery is crucial.

Innovation Solution

The use of Tris as a buffer significantly enhances finafloxacin's solubility and stability, allowing for the creation of pharmaceutically acceptable parenteral compositions with high finafloxacin concentrations, maintaining stability over time and preventing pH drops during storage or dilution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If finafloxacin is formulated in physiological solvents, then the composition can be used for parenteral administration, but the solubility is insufficient to generate stable solutions of high enough concentration

Engineering Contradiction:
Improveconcentration of finafloxacinVSAvoidphysical stability of solution
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical composition parameters by introducing Tris buffer and adjusting pH to 8.0-8.5, which fundamentally alters the solubility characteristics of finafloxacin. This parameter change enables the solution to maintain both high concentration (1-6 g/l) and long-term physical stability without particle formation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Tris buffer acts as an intermediary substance that mediates between finafloxacin and the aqueous environment. It facilitates enhanced solubility through buffer interactions while maintaining solution stability, effectively bridging the gap between the drug molecule and physiological conditions

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If finafloxacin is formulated at high concentrations for effective treatment, then therapeutic efficacy is improved, but particle formation occurs during storage

Engineering Contradiction:
Improveamount of finafloxacinVSAvoidstorage stability
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

By changing the pH parameter to 8.0-8.5 and incorporating Tris buffer, the patent transforms the chemical environment to prevent degradation and particle formation. This enables reliable storage of high-concentration finafloxacin solutions (1-6 g/l) without compromising stability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The formulation proactively addresses potential instability by incorporating Tris buffer and optimizing pH before storage occurs. This preemptive approach cushions against degradation and particle formation that would otherwise occur during storage of high-concentration solutions

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Volume of stationary object

If finafloxacin is administered in acceptable volumes, then patient compliance is improved, but the solubility limits the amount of active compound that can be administered

Engineering Contradiction:
Improvevolume of parenteral solutionVSAvoidamount of finafloxacin
Core Design Contradiction:
Volume of stationary objectVSQuantity of substance

Solution Approach 1:

The patent changes the solvent composition parameters by introducing Tris buffer and adjusting pH, which increases finafloxacin solubility by several-fold. This enables administration of higher amounts of active compound (1-6 g/l) in clinically acceptable volumes without compromising solubility

Inventive Principle:
Principle #35Parameter changes

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

Tris-based compositions achieve a 3-4-fold increase in finafloxacin solubility and long-term stability, enabling effective treatment of bacterial infections with improved bioavailability and reduced particle formation, as demonstrated by increased solubility and therapeutic efficacy in clinical and preclinical studies.

Implementation Method 1

it was found that finafloxacin has a high solubility in the presence of Tris

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 2

maintaining stability over time and preventing pH drops during storage or dilution

Methodology Applied
Scientific EffectBuffering:

Data Source

PatentUS10576088B2Compositions comprising finafloxacin and Tris
Publication Date: 2020.03.03 MERLION GMBH

AI summary

It was found that finafloxacin has a high solubility in the presence of Tris. Such solubility is significantly higher than in the presence of other compounds typically used as buffers (e.g. phosphate buffer). The observed significant increase in solubility of finafloxacin in compositions comprising Tris is further advantageously accompanied by a long term stability of such solutions. Tris is therefore to be regarded as a specific tool to considerably enhance the solubility of finafloxacin in solutions. By preparing compositions comprising Tris it is possible to dissolve finafloxacin in such an amount therein that these compositions can effectively be used as parenteral compositions for the treatment of bacterial infections.