Foxy-5 Hexapeptide Salt Compositions for Solubility and Stability
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Solution Overview
Problem
The limited solubility of Foxy-5 in water limits production throughput, and its conversion to the trisodium salt, while increasing solubility, results in instability, making it unsuitable as a drug substance.
Innovation Solution
Foxy-5 forms highly soluble compositions with various nitrogen bases, including ammonia, quaternary ammonium hydroxides, alkylated guanidines, amino acids, and primary/secondary amines, forming mono-, di-, and tri-salts, which are subjected to a thermocycling process to enhance stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Foxy-5 is converted to the trisodium salt to increase solubility, then solubility is improved, but stability deteriorates
Solution Approach 1:
The patent applies parameter changes by systematically varying the cation type (from sodium to ammonium and organic cations like choline, glucamine, and tromethamine) and the stoichiometric ratio (mono-, di-, and tri-salts) to optimize both solubility and stability. This approach identified that while trisodium salt has high solubility, it suffers from instability, whereas triammonium and certain organic cation salts achieve both high solubility (>20 g/L) and improved stability through controlled parameter modification.
2Productivity
If the product concentration for lyophilization is increased to improve productivity, then production throughput is improved, but solubility limitations worsen
Solution Approach 1:
The patent resolves this contradiction by changing the chemical parameters of the Foxy-5 compound itself - specifically by forming salt compositions with different cations (ammonium, organic cations) that have fundamentally different solubility characteristics. These salt forms enable high product concentrations (≥20 g/L) during lyophilization that were previously unachievable with the free acid form, thereby directly increasing production throughput without compromising solubility.
3Ease of manufacture
If Foxy-5 is used as a salt-free drug substance, then manufacturing simplicity is maintained, but solubility deteriorates
Solution Approach 1:
The patent applies the composite materials principle by creating salt compositions that combine Foxy-5 (the active pharmaceutical ingredient) with various cations (ammonium, organic cations such as choline, glucamine, tromethamine). These composite salt forms maintain the therapeutic activity of Foxy-5 while providing significantly enhanced solubility properties. The salt compositions can be manufactured through straightforward processes like co-lyophilization or spray drying, preserving manufacturing simplicity while achieving the desired solubility enhancement.
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 new compositions exhibit improved solubility and stability, allowing for increased production throughput and suitability as a drug substance.
Implementation Method 1
Foxy-5 forms highly soluble compositions with various nitrogen bases, including ammonia, quaternary ammonium hydroxides, alkylated guanidines, amino acids, and primary/secondary amines, forming mono-, di-, and tri-salts
Implementation Method 2
the resulting solid composition of step c) is further subjected to a thermocycling process
Data Source
AI summary
The present disclosure relates to new, highly soluble compositions of the Wnt hexapeptide Foxy-5. The present disclosure further relates to methods for the production of said compositions and stability assessments thereof.