Mixed Solvent System for Poorly Soluble Drug Microparticles
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Solution Overview
Problem
Current methods for producing microparticles containing poorly soluble drugs face challenges such as low encapsulation efficiency, loss of the drug during processing, and residual organic solvent issues, particularly when using solvents like dichloromethane, which require large amounts and complicate the production process.
Innovation Solution
A method involving a mixed solvent system with at least two organic solvents, including a first solvent like dichloromethane and a co-solvent with specific properties, such as diethyl ether, to enhance solubility and facilitate the removal of residual solvents, while maintaining a laminar flow in microfluidic processes for uniform microparticle production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If a large amount of dichloromethane solvent is used to dissolve poorly soluble drugs, then the solubility of the drug is improved, but the possibility of residual organic solvent remaining increases and the encapsulation efficiency of the drug decreases
Solution Approach 1:
The patent changes the chemical composition parameter of the solvent system by introducing a co-solvent (ether or ester) with specific properties (boiling point 30-70°C, water solubility 10-50 g/100 mL) to work synergistically with dichloromethane. This parameter change enables reduced total solvent quantity while maintaining drug solubility and facilitating solvent removal, thereby resolving the contradiction between solubility improvement and residual solvent reduction.
2Ease of operation
If the content of organic solvent is increased to control viscosity of the oil phase solution, then the ease of operation is improved, but the possibility of loss of poorly soluble drug increases and the possibility for residual organic solvent to remain increases
Solution Approach 1:
The patent modifies the physical parameter of the solvent system by selecting co-solvents with specific boiling points (30-70°C) and water solubilities (10-50 g/100 mL). These parameter changes enable effective viscosity control at lower total solvent concentrations, while the specific boiling point range facilitates easy removal without causing drug loss or residual solvent problems.
3Ease of manufacture
If the solvent evaporation method is used to remove volatile solvent, then the ease of manufacture is improved and the time is reduced, but the encapsulation efficiency of the drug decreases due to drug loss at increased temperature
Solution Approach 1:
The patent selects co-solvents with low boiling points (30-70°C) that enable solvent removal at lower temperatures compared to conventional solvents. This parameter change allows the use of simple evaporation methods while preserving drug integrity and encapsulation efficiency, as the lower removal temperature prevents drug degradation and loss.
4Manufacturing precision
If the solvent extraction method is used to remove non-volatile solvent, then the encapsulation efficiency is maintained, but the device complexity and time increase
Solution Approach 1:
The patent exploits phase transition (evaporation) by selecting co-solvents with specific boiling points (30-70°C) that enable easy vaporization. This allows replacement of complex extraction processes with simple evaporation, maintaining encapsulation efficiency while dramatically reducing device complexity and processing time.
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
This approach achieves high encapsulation efficiency (>90%) with reduced residual organic solvents, producing uniform and high-quality microparticles by improving solubility and solvent removal efficiency, thus overcoming previous limitations in drug loading and production complexity.
Implementation Method 1
preparing an oil phase solution by dissolving a poorly soluble drug and a biodegradable polymer in a mixed solvent comprising at least two organic solvents
Implementation Method 2
the co-solvent has a boiling point of 50°C or lower, and thus even if the temperature is increased during the process of removing the organic solvent, the co-solvent can be removed before the drug is lost
Data Source
AI summary
A method for producing microparticles containing a poorly soluble drug, and microparticles produced by the method are proposed. According to the method for preparing microparticles, it is possible to produce microparticles that are uniform and of good quality and have high encapsulation efficiency for the poorly soluble drug and low contents of residual organic solvents, by using at least two organic solvents.