Continuous Droplet Dehydration for Uniform Low-Void Biologic Particles
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Solution Overview
Problem
Current methods for forming circular particles with therapeutic biologics lack sufficient control over size uniformity, shape selectivity, and surface functionality, resulting in inefficient production of particles with high internal void spaces.
Innovation Solution
A method involving continuous droplet formation and dehydration of aqueous liquid droplets comprising a therapeutic biologic, followed by removal of the liquids, to produce circular particles with less than 10% internal void spaces and circularity from 0.80 to 1.00, controlled by the Peclet number of the mixture.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional particle formation methods are used, then production efficiency is improved, but control over size uniformity and shape selectivity deteriorates
Solution Approach 1:
The particle formation process is segmented into distinct stages: droplet generation in a first continuous phase, dehydration in a second continuous phase, and final particle formation. This segmentation allows independent optimization of each stage for both productivity and precision, resolving the contradiction between production efficiency and manufacturing precision.
Solution Approach 2:
The system employs dynamic control of flow rates for the aqueous droplet phase, first continuous phase, and second continuous phase. By dynamically adjusting these flow rates, the process maintains high productivity while achieving precise control over particle size uniformity and circularity through the Peclet number.
2Device complexity
If internal void spaces are increased in particles, then manufacturing complexity is reduced, but therapeutic biologic stability deteriorates
Solution Approach 1:
The continuous dehydration process through the second continuous phase eliminates internal void spaces by maintaining continuous action throughout particle formation. This continuous process achieves low void space (<10%) and high circularity (0.80-1.00) without requiring complex post-processing, thereby maintaining therapeutic biologic stability while avoiding increased manufacturing complexity.
3Manufacturing precision
If particle circularity is increased to 0.80-1.00, then surface functionality is improved, but production efficiency deteriorates
Solution Approach 1:
The process utilizes parameter changes in the Peclet number by adjusting flow rates of different phases to achieve the desired circularity range (0.80-1.00). This parameter optimization allows the system to produce highly circular particles with improved surface functionality while maintaining efficient continuous production, resolving the contradiction between manufacturing precision and productivity.
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 method enables the production of stable, pharmaceutically relevant particles with controlled morphology and low internal void spaces, enhancing the stability and functionality of therapeutic biologics for pharmaceutical applications.
Implementation Method 1
contacting the aqueous first liquid comprising the therapeutic biologic with an organic second liquid by a continuous process, thereby forming a mixture comprising aqueous liquid droplets
Implementation Method 2
dehydrating the aqueous liquid droplets in the mixture; and removing the aqueous first liquid and organic second liquid from the mixture
Data Source
AI summary
The present disclosure relates to methods that enable the continuous formation of droplets and dehydration of droplets to provide pharmaceutically relevant particles that can be used for therapy. In particular, the methods disclosed herein allow the controlled continuous droplet formation and dehydration that produce circular particles having low internal void spaces comprising bioactive therapeutic biologics.