Continuous Double Emulsion Microparticle Encapsulation

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Solution Overview

Problem

Traditional methods for microparticle encapsulation of water-soluble bioactive agents are often cumbersome and time-consuming due to discontinuous processing, leading to inefficiencies and variability in the encapsulation process.

Innovation Solution

A continuous process for forming microparticles involving the formation of a water-in-oil emulsion followed by a water-in-oil-in-water double emulsion, where the first and second phases are continuously mixed to minimize batch processing and enhance reproducibility and bioactive agent loading efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If discontinuous processing methods are used for microparticle encapsulation, then the process can be performed with simpler equipment, but the encapsulation process becomes time-consuming and exhibits variability

Engineering Contradiction:
Improveprocess simplicityVSAvoidencapsulation efficiency
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The patent implements continuous processing where the aqueous phase containing the bioactive agent, organic phase, and second aqueous phase are continuously mixed and processed through the emulsification system without batch interruptions. This continuous flow approach eliminates the time-consuming batch preparation steps while maintaining encapsulation efficiency, directly resolving the contradiction between process simplicity and productivity

Inventive Principle:
Principle #20Continuity of useful action

2Device complexity

If discontinuous batch processing is used, then equipment requirements are reduced, but reproducibility and consistency of microparticle morphology are compromised

Engineering Contradiction:
Improveequipment requirementsVSAvoidmicroparticle morphology consistency
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The continuous processing system maintains steady-state operation with controlled flow rates of all phases, ensuring consistent mixing conditions and emulsion formation throughout the process. This continuity eliminates the variability inherent in batch processing while achieving reproducible microparticle morphology, resolving the contradiction between equipment complexity and manufacturing precision

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The system incorporates controlled feedback mechanisms where the flow rates and mixing parameters are regulated to maintain consistent processing conditions. This feedback control ensures that variations in input materials are compensated for, maintaining uniform microparticle morphology and encapsulation efficiency throughout continuous operation

Inventive Principle:
Principle #23Feedback

3Quantity of substance

If traditional double emulsion methods are used, then the encapsulation of water-soluble bioactive agents is achieved, but significant loss of bioactive agent occurs during processing

Engineering Contradiction:
Improvebioactive agent encapsulationVSAvoidbioactive agent loss
Core Design Contradiction:
Quantity of substanceVSLoss of substance

Solution Approach 1:

The continuous processing system minimizes the time that the bioactive agent is exposed to potentially degrading conditions during emulsion formation and solvent removal. By continuously moving the emulsion through the processing stages without batch interruptions, the system reduces bioactive agent loss while maintaining high encapsulation efficiency, directly addressing the contradiction between quantity encapsulated and quantity lost

Inventive Principle:
Principle #20Continuity of useful action

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 continuous process results in more consistent microparticle morphology and reduced initial burst release of bioactive agents, improving the control and reproducibility of the encapsulation process while minimizing bioactive agent loss.

Implementation Method 1

removing the organic phase from the double emulsion, thereby forming microparticles

Methodology Applied
Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Data Source

PatentEP2389160B1Continuous double emulsion process for making microparticles
Publication Date: 2017.09.13 EVONIK CORPORATION
  • EP2389160B1 patent drawingFigure 1a~1b
  • EP2389160B1 patent drawingFigure 1c~2a
  • EP2389160B1 patent drawingFigure 2b

AI summary

Described herein are improved methods for microparticle encapsulation. In one aspect, the disclosed methods comprise a substantially continous double emulsion process. In a further aspects, microparticles comprising a bioactive agent therein are made by the disclosed methods.