Glatiramer Acetate Microparticle Solvent Removal
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Solution Overview
Problem
Existing processes for preparing microparticles containing glatiramer acetate result in high levels of residual organic solvents like dichloromethane, which are toxic and carcinogenic, violating regulatory limits for pharmaceutical compositions.
Innovation Solution
A modified double emulsification process involving the application of vacuum and/or air stream during solvent evaporation in the water-in-oil-in-water double emulsion step to reduce residual organic solvent levels to regulatory-acceptable limits without compromising the microparticles' morphology, binding percentage, or release profile.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If traditional solvent evaporation method is used, then microparticle formation is achieved, but residual organic solvent levels are high (toxic and carcinogenic)
Solution Approach 1:
The patent extracts and removes the harmful organic solvent (dichloromethane) from the microparticle system through enhanced evaporation methods. The process specifically targets and eliminates the residual solvent while preserving the therapeutic microparticle structure, reducing solvent levels from problematic concentrations to below 600 ppm.
Solution Approach 2:
The patent changes the evaporation parameters by applying vacuum conditions and/or air streams during the solvent removal step. This modifies the physical conditions of evaporation to accelerate solvent removal and achieve regulatory compliance levels while maintaining microparticle integrity.
2Object-affected harmful factors
If vacuum and air stream are applied during evaporation, then residual solvent levels are reduced, but process complexity increases
Solution Approach 1:
The patent employs pneumatic methods by introducing air streams during the evaporation process to enhance solvent removal. This uses gas flow dynamics to accelerate dichloromethane evaporation and achieve regulatory compliance levels more effectively than passive evaporation alone.
Solution Approach 2:
The patent creates a controlled atmospheric environment during evaporation by applying vacuum and/or introducing air streams. This modified atmosphere facilitates faster and more complete solvent removal while protecting the microparticle formulation from degradation.
3Object-affected harmful factors
If extended evaporation time is used, then residual solvent levels are reduced, but manufacturing time increases
Solution Approach 1:
The patent applies preliminary action by implementing vacuum and air stream conditions during the evaporation phase to accelerate solvent removal. This proactive approach to solvent elimination reduces the time required to achieve regulatory compliance levels compared to traditional extended evaporation methods.
Solution Approach 2:
The patent exploits phase transition dynamics by using vacuum and air streams to enhance the evaporation (liquid to gas) of dichloromethane. This accelerates the phase transition process, rapidly reducing residual solvent levels without requiring extended processing times.
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 process effectively reduces residual organic solvent levels in microparticles to below 600 ppm, ensuring compliance with regulatory standards while maintaining therapeutic efficacy and reducing side effects, thus providing a safer and more effective long-acting parenteral composition for multiple sclerosis treatment.
Implementation Method 1
The organic solvent is slowly evaporated by stirring the double emulsion in a fume hood
Implementation Method 2
application of vacuum and/or air stream to the double water-in-oil-in-water double emulsion results in a product having reduced levels of organic solvent
Data Source
AI summary
The present invention provides an improved process for preparing microparticles containing glatiramer acetate having low levels of residual organic solvent(s), in particular dichloromethane. The microparticles are incorporated into long acting parenteral pharmaceutical compositions in depot form that are suitable for subcutaneous or intramuscular implantation or injection, and that may be used to treat multiple sclerosis.