Solid Bead Formation via Piezoelectric Droplet Generation

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Solution Overview

Problem

Existing methods for producing solid beads with pharmaceutically active ingredients face challenges in predicting and controlling drug release profiles due to polydispersity and difficulties in scaling up production processes, particularly when using techniques like piezoelectric dispensers and microfluidic devices.

Innovation Solution

A method involving a liquid droplet generator with a piezoelectric component to form droplets of a polymer solution, which are then passed through a gas into contact with a solvent-miscible second liquid, allowing rapid solvent extraction to form solid beads with controlled size and uniformity, achieving a coefficient of variation of less than 0.1 in the greatest dimension.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If solvent extraction is performed slowly over hours, then complete extraction is achieved, but production time is excessive and productivity is low

Engineering Contradiction:
Improveextraction completenessVSAvoidproduction speed
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent changes the parameter of solvent miscibility by selecting a second liquid that is substantially miscible with the solvent (solubility at least 5g/100ml). This parameter change enables rapid extraction kinetics while maintaining complete solvent removal, resolving the contradiction between extraction completeness and production speed

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces a second liquid as an intermediary medium that facilitates rapid solvent extraction. This intermediary liquid acts as a bridge between the polymer solution and the final solid bead, enabling fast mass transfer of the solvent without compromising extraction completeness

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If beads are produced using conventional methods, then production is achievable, but beads are polydisperse and drug release profile cannot be predicted or controlled

Engineering Contradiction:
Improveproduction capabilityVSAvoidbead size uniformity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent replaces mechanical mixing and conventional bead formation methods with a droplet-based microfluidic approach. Liquid droplets of defined size are generated and solidified, substituting uncontrolled mechanical processes with precisely controllable fluid dynamics, resulting in monodisperse beads with predictable drug release

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the concentration parameter by using at least 10% w/v polymer concentration in the first liquid. This high concentration ensures rapid solidification upon contact with the second liquid, locking in the droplet size and producing uniform monodisperse beads

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If microfluidic devices are used to produce consistent sized beads, then bead uniformity is achieved, but device complexity increases and scaling up for commercial production becomes difficult

Engineering Contradiction:
Improvebead size consistencyVSAvoiddevice scalability
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent segments the bead production process into distinct functional zones: droplet generation, solvent extraction, and bead collection. This segmentation allows each zone to be optimized independently and facilitates scaling by simply increasing the length of the linear device rather than increasing complexity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent transitions from complex three-dimensional microfluidic networks to a simplified linear one-dimensional device architecture. The process occurs along a single flow direction with sequential zones, dramatically reducing device complexity while maintaining bead uniformity and enabling easy scaling by extending the device length

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

4Ease of operation

If polymer concentration is low in the first liquid, then droplet formation is easier, but beads are polydisperse and release profile control is poor

Engineering Contradiction:
Improvedroplet formationVSAvoidbead monodispersity
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent changes the concentration parameter to at least 10% w/v polymer in the first liquid. This high concentration creates highly viscous droplets that maintain their shape during solvent extraction, preventing coalescence and ensuring monodisperse bead formation while still allowing controlled droplet generation

Inventive Principle:
Principle #35Parameter changes

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 monodisperse solid beads with high encapsulation efficiency and controlled release characteristics, facilitating predictable drug delivery and scalable commercial production.

Implementation Method 1

the liquid droplet generator (3) comprises a piezoelectric component operable to generate liquid droplets

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 2

Passing the liquid droplets through a gas into contact with a second liquid so as to cause the solvent to exit the droplets, thus forming solid beads; the solubility of the solvent in the second liquid being at least 5g of solvent per 100ml of second liquid

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

Data Source

PatentEP2632581B1Method of making solid beads
Publication Date: 2020.03.04 MIDATECH PHARMA (WALES) LTD
  • EP2632581B1 patent drawingFigure 1~2B
  • EP2632581B1 patent drawingFigure 3
  • EP2632581B1 patent drawingFigure 4

AI summary

A method of forming solid beads, the method comprising: Providing a first liquid comprising a solute and a solvent Forming liquid droplets of the first liquid Contacting the liquid droplets with a second liquid so as to cause the solvent to exit the droplets, thus forming solid beads, the solute comprising a polymer, the concentration of polymer in the first liquid being at least 7% w/v., the solubility of the solvent in the second liquid being at least 5g of solvent per 100ml of second liquid.