Aqueous Micafungin Composition for Extended Storage Stability
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Solution Overview
Problem
Micafungin compositions, particularly in aqueous solutions, suffer from instability and rapid degradation, limiting their storage stability and requiring complex aseptic compounding processes, which increases the risk of contamination and medication errors.
Innovation Solution
Aqueous pharmaceutical compositions comprising micafungin are formulated with specific pH ranges (3.0 to 7.0) and concentrations, avoiding lyoprotectants like disaccharides, and using suitable buffering and tonicity agents to create ready-to-use or concentrate formulations that maintain stability for extended periods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If micafungin is formulated as an aqueous solution for parenteral administration, then ease of administration and elimination of aseptic compounding is improved, but storage stability deteriorates due to rapid degradation
Solution Approach 1:
The patent applies parameter changes by optimizing the pH range (3.0-7.0) and concentrations of buffering agents (0.1-400 mM) and tonicity adjusting agents (0-500 mg/mL) to achieve both stability and ease of administration. This resolves the contradiction by finding the optimal parameter space where the composition remains stable in aqueous form without requiring lyophilization while still preventing rapid degradation.
2Stability of the object's composition
If lyoprotectants like disaccharides are used to stabilize micafungin in aqueous solution, then storage stability is improved, but the composition becomes less ready-to-use and requires additional formulation steps
Solution Approach 1:
The patent extracts and eliminates disaccharide lyoprotectants from the formulation, achieving stability through optimized pH and tonicity parameters alone. This resolves the contradiction by removing unnecessary components that would complicate the formulation while maintaining stability through the identified optimal parameter ranges.
Solution Approach 2:
The patent uses simple, readily available buffering agents and tonicity adjusting agents instead of complex lyoprotectants, creating a formulation that is easier to manufacture and more ready-to-use while achieving comparable or superior stability.
3Stability of the object's composition
If complex aseptic compounding processes are required to prepare micafungin for administration, then storage stability is maintained, but the risk of contamination and medication errors increases
Solution Approach 1:
The patent performs preliminary action by pre-formulating micafungin in stable aqueous solutions with optimized pH and tonicity parameters during manufacturing. This eliminates the need for complex aseptic compounding at the point of use, thereby maintaining stability while significantly reducing contamination risk and medication errors.
Data Source
AI summary
An aqueous pharmaceutical composition suitable for parenteral administration and having enhanced storage stability includes between about 0.1 mg/mL and about 40 mg/mL micafungin; (ii) between about 0.1 mM and 400 mM buffering agent; and (iii) between about 0 mg/mL and about 500 mg/mL tonicity adjusting agent, wherein the pH of the composition is between about 3.0 and 7.0, for example, between about 3.5 and 7.0.