Micafungin Aqueous 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 can lead to microbiological contamination and medication errors.
Innovation Solution
Aqueous pharmaceutical compositions comprising micafungin with specific pH and tonicity adjusting agents, formulated to be ready-to-use or concentrate, ensuring stability and eliminating the need for additional compounding, with pH between 3.0 and 7.0, and containing buffering agents like sodium citrate and tonicity adjusting agents like sodium chloride or dextrose.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If micafungin is formulated as an aqueous solution, then ease of administration 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 buffer concentration (0.1-400 mM) of the aqueous micafungin composition to achieve both stability and ease of administration. This resolves the contradiction by modifying chemical parameters to simultaneously improve administrability while preventing degradation.
Solution Approach 2:
The patent introduces buffering agents (0.1-400 mM) as intermediaries that mediate between the micafungin molecule and the aqueous environment. These buffers act as protective intermediaries that maintain pH stability and prevent micafungin degradation, enabling both aqueous formulation and storage stability.
2Loss of time
If micafungin is stored in aqueous solution for extended periods, then convenience is improved, but degradation increases
Solution Approach 1:
The patent extends storage time by changing key parameters including pH (3.0-7.0) and buffer concentration (0.1-400 mM). These parameter modifications create an optimized aqueous environment that maintains micafungin stability over extended storage periods, resolving the time-stability contradiction.
Solution Approach 2:
The patent applies preliminary action by pre-formulating micafungin in a stabilized aqueous composition with appropriate buffers and pH adjustment before storage. This preliminary optimization of formulation parameters prevents degradation during storage, enabling extended stability without compounding.
3Stability of the object's composition
If complex aseptic compounding processes are used, then storage stability is improved, but risk of contamination increases
Solution Approach 1:
The patent extracts the compounding step from the storage and administration process by providing micafungin in a pre-formulated, stabilized aqueous composition. This eliminates the need for separate aseptic compounding operations, thereby removing the contamination risk associated with multiple handling steps while maintaining stability.
Solution Approach 2:
The patent merges the stabilization function into the formulation itself by incorporating buffers and pH adjustment directly into the aqueous micafungin composition. This consolidation of stabilization measures into the final product eliminates the need for separate compounding procedures, reducing contamination risk while maintaining stability.
4Stability of the object's composition
If lyophilized form is used, then storage stability is improved, but device complexity increases due to reconstitution requirements
Solution Approach 1:
The patent extracts the reconstitution step from the administration process by providing micafungin in a ready-to-use aqueous formulation. This eliminates the need for lyophilized powder reconstitution, simplifying the device/process while maintaining stability through optimized formulation parameters rather than physical state.
Solution Approach 2:
The patent inverts the conventional approach by formulating micafungin as a stable aqueous solution rather than a lyophilized powder. This inversion of the physical state, combined with optimized pH and buffer parameters, achieves stability without requiring complex reconstitution procedures.
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 compositions demonstrate enhanced storage stability, allowing for extended storage periods without significant degradation, reducing the risk of contamination and medication errors, and facilitating convenient administration.
Implementation Method 1
between about 0.1 mM and 400 mM buffering agent, for example, between about 0.5 mM and 400 mM... the composition having a pH between about 3.0 and about 7.0
Implementation Method 2
between about 0 mg/mL and about 500 mg/mL tonicity adjusting agent... containing buffering agents like sodium citrate and tonicity adjusting agents like sodium chloride or dextrose
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.