Micafungin Sodium Solvate Crystallization Stability
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Solution Overview
Problem
Micafungin sodium, an anti-fungal drug, has poor stability and is difficult to crystallize, leading to quality issues during transportation and storage, and existing methods for obtaining stable forms are limited, hindering its pharmaceutical development.
Innovation Solution
A solvate of micafungin sodium is developed, comprising 2 molecules of crystalline water and 0.5 molecule of methanol, which forms column-like crystals with improved stability and ease of filtration, using a three-phase solvent system and specific crystallization conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If the compound of formula I is precipitated by adding acetone and ethyl acetate to give amorphous form, then the compound can be obtained, but the stability is poor and quality is affected by degraded products during transportation or long-term preservation
Solution Approach 1:
The patent changes the physical state parameter of the compound from amorphous to crystalline form by controlling crystallization conditions (solvent system, temperature, pH), thereby improving stability while maintaining quality
Solution Approach 2:
The patent creates a composite crystalline structure incorporating the compound of formula I with specific solvents (acetone, ethyl acetate, isopropanol, water) in defined ratios to form a stable solvate with improved reliability
2Stability of the object's composition
If the compound of formula I is crystallized, then stability is improved, but it is difficult to crystallize and generally remains amorphous
Solution Approach 1:
The patent uses specific solvents (acetone, ethyl acetate, isopropanol, water) as intermediaries to facilitate crystallization of the compound of formula I, transforming it from difficult-to-crystallize amorphous form to stable crystalline form through controlled solvation and crystallization processes
Solution Approach 2:
The patent changes manufacturing parameters including solvent composition ratios, temperature ranges (0-25°C), and pH conditions to enable crystallization while maintaining ease of manufacture
3Quantity of substance
If the content of solvent in the precipitate is reduced below standard by extending drying time, then solvent content is reduced, but the degraded products increase and quality is reduced
Solution Approach 1:
The patent optimizes drying parameters (temperature, time, pressure) to achieve the desired solvent content reduction while minimizing degradation, balancing quantity and quality requirements
4Shape
If needle-like crystals of B82 type are obtained, then crystal form is achieved, but filtration is difficult and operation time is long
Solution Approach 1:
The patent changes crystallization parameters (solvent system, temperature, pH) to produce crystals with improved morphology that are easier to filter while maintaining the desired crystal form characteristics
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 solvate provides a stable form of micafungin sodium, facilitating easier production and storage, and can be converted to solvent-free crystals, enhancing its stability and usability in various pharmaceutical formulations.
Implementation Method 1
a solvate of micafungin sodium is developed, comprising 2 molecules of crystalline water and 0.5 molecule of methanol, which forms column-like crystals with improved stability and ease of filtration, using a three-phase solvent system and specific crystallization conditions
Data Source
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AI summary
Provided in the invention is a solvate of a cyclic peptide compound, represented byformula I is the structural formula of the cyclic peptide compound, and, also disclosed are a preparation method for same and uses thereof.