Daptomycin Formulations Stabilized by Amino Acids
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Daptomycin is susceptible to hydrolytic degradation and aspartyl transpeptidation, leading to the formation of degradation products that reduce its stability and efficacy.
Innovation Solution
The development of stable pharmaceutical formulations comprising daptomycin and at least one amino acid, such as alanine, arginine, or histidine, or their pharmaceutically acceptable salts or derivatives, which retard the formation of degradation products and improve storage conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If daptomycin is stored under conventional conditions, then it maintains its antibacterial activity, but it undergoes hydrolytic degradation and aspartyl transpeptidation leading to formation of degradation products
Solution Approach 1:
Amino acids (alanine, arginine, histidine) or their salts are introduced as intermediary substances that interact with daptomycin to form stable complexes. These intermediaries prevent direct hydrolytic degradation and aspartyl transpeptidation by stabilizing the daptomycin molecule, thereby reducing the formation of degradation products while maintaining antibacterial activity.
Solution Approach 2:
The invention changes the chemical environment parameters by introducing amino acids with specific properties (basic amino acids like arginine and histidine, or neutral amino acids like alanine). These parameter changes in the formulation composition alter the degradation kinetics, reducing hydrolytic degradation and transpeptidation rates, thus improving daptomycin stability without compromising its therapeutic effect.
2Stability of the object's composition
If daptomycin is formulated with amino acids to improve stability, then degradation is retarded, but the formulation complexity increases
Solution Approach 1:
The invention simplifies the formulation approach by making a single key parameter change: introducing amino acids or their salts at specific concentrations (0.1-100 mM range). This single parameter modification provides comprehensive stabilization against multiple degradation pathways (hydrolysis and transpeptidation) without requiring complex multi-component systems, thus improving chemical stability while minimizing formulation complexity.
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 exhibit improved chemical and physical stability, maintaining daptomycin's efficacy and potency, and allowing for more flexible storage and handling conditions.
Implementation Method 1
Daptomycin is susceptible to hydrolytic degradation and is known to degrade by aspartyl transpeptidation at asp-9 residue in mildly acidic solutions.
Implementation Method 2
Daptomycin is susceptible to hydrolytic degradation and is known to degrade by aspartyl transpeptidation at asp-9 residue in mildly acidic solutions.
Implementation Method 3
The development of stable pharmaceutical formulations comprising daptomycin and at least one amino acid, such as alanine, arginine, or histidine, or their pharmaceutically acceptable salts or derivatives, which retard the formation of degradation products and improve storage conditions.
Data Source
AI summary
The present invention relates to compositions comprising daptomycin and at least one amino acid, methods of providing such compositions and the uses thereof.