Bioresorbable Polyester Purification for Controlled Release
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Solution Overview
Problem
Existing controlled release pharmaceutical compositions using bioresorbable polyesters suffer from high initial burst effects, long lag times, and rapid drops in drug release rates, leading to undesirable side effects and inconsistent therapeutic delivery.
Innovation Solution
A purification method for bioresorbable polyesters is developed, involving dissolution in organic solvents with heteroatoms and precipitation with alcohols to reduce metal content to <40 ppm, resulting in improved controlled release profiles by minimizing residual metal catalysts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If bioresorbable polyesters are produced using metal catalysts, then polymerisation efficiency is improved, but residual metal content increases causing burst effects and long lag times
Solution Approach 1:
The patent removes the harmful metal catalysts from the polyester structure through a purification process involving dissolution in dichloromethane and precipitation in methanol. This extraction eliminates residual metals that cause burst effects and lag times, while maintaining the polymerisation efficiency benefits of using metal catalysts during production.
Solution Approach 2:
The patent changes the metal content parameter from typical levels (>10 ppm) to extremely low levels (<1 ppm) through purification. This parameter change resolves the contradiction by eliminating the harmful effects of residual metals while preserving the production efficiency advantages of metal-catalysed polymerisation.
2Manufacturing precision
If existing purification methods are used, then metal content is reduced to <10 ppm, but burst effects and lag times persist
Solution Approach 1:
The patent achieves a more stringent metal content parameter (<1 ppm) compared to conventional purification (<10 ppm). This enhanced parameter control eliminates the residual metal effects that cause burst release and lag time, thereby improving drug release profile reliability while maintaining manufacturing precision.
Solution Approach 2:
The patent uses a proven purification methodology (dissolution-precipitation) but applies it with optimized parameters and conditions to achieve superior metal removal. This approach copies the effective mechanism while improving the outcome to eliminate burst effects and lag times.
3Adaptability or versatility
If polymeric microparticles are used for controlled release, then drug delivery is targeted, but high initial burst effect occurs
Solution Approach 1:
The patent removes the source of burst effects (residual metal catalysts) from the polyester matrix used in polymeric microparticles. This extraction allows the microparticles to maintain their targeted drug delivery capability while eliminating the harmful initial burst effect caused by metal-catalysed polymer degradation.
Solution Approach 2:
The patent converts the harmful effect of residual metals into a benefit by using extreme purification to remove them. The very property that caused burst effects (metal-catalysed polymer structure) is addressed through purification, allowing the microparticles to achieve both targeted delivery and controlled release without burst effects.
Data Source
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AI summary
Provided herein is a bioresorbable polyester wherein the metal content of the polyester is > 0 ppm and < 40ppm, a controlled release pharmaceutical composition containing such polyesters, and a kit for injecting a controlled release pharmaceutical composition. Also provided herein is a method of purifying a bioresorbable polyester with a metal content > 0 ppm comprising the steps of: i) dissolving the polyester in an organic solvent to form a polyester-solvent solution, wherein the organic solvent comprises at least one heteroatom selected from oxygen, nitrogen, sulphur and phosphorus; ii) precipitating the polyester from the polyester-solvent solution by combining the polyester-solvent solution with an organic non-solvent, said non-solvent being an alcohol; and (iii) separating the precipitated polyester from the solvent and non-solvent to obtain a purified polyester.