Tangential Flow Filtration for Shear Sensitive Materials

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Solution Overview

Problem

Conventional manufacturing processes for shear sensitive materials, such as N'-(3,4-dichlorobenzyl)-N5-octyl-biguanide gluconate, face challenges including clogged filters, low permeate flow rates, and high manual intervention due to the need for filtration and handling of slurries, which limits efficiency and scalability.

Innovation Solution

A self-contained, automated process using a tangential flow filtration system with multiple filters in series and a circulating process stream that allows continuous filtration and minimizes manual handling, enabling higher permeate flow rates and reducing shear on the product through backflushing and recirculation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional filtration system is used where product feed stream flows through filter pores, then filtration removes impurities, but permeate flow rate becomes low and pores become clogged

Engineering Contradiction:
Improvefiltration effectivenessVSAvoidpermeate flow rate
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent inverts the traditional filtration approach by using tangential flow filtration where the feed stream flows parallel to the filter membrane surface rather than directly through the pores. This reversal prevents particle accumulation in pores, maintains high permeate flow rates, and eliminates clogging while still achieving effective impurity removal through the pressure-driven filtration process

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent changes the flow direction parameter from perpendicular (traditional filtration) to parallel (tangential flow filtration) relative to the membrane surface. This parameter change transforms the filtration mechanism to prevent pore clogging while maintaining filtration effectiveness, and allows for continuous operation with sustained high permeate flow rates

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If agitation of starting slurry is performed in process vessel, then mixing is achieved, but particle size decreases and filter pores become clogged

Engineering Contradiction:
Improvemixing efficiencyVSAvoidfiltration performance
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent applies preliminary action by performing tangential flow filtration on the slurry before any agitation that might reduce particle size. The filtration process is set up to handle the as-received slurry particles in their original size distribution, preventing the need for aggressive agitation that would fragment particles and clog filters

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent extracts the filtration step from the traditional sequence where agitation precedes filtration. By using tangential flow filtration, the system can separate impurities from the slurry without requiring intensive agitation, thus taking out the harmful agitation step while maintaining mixing through gentler means

Inventive Principle:
Principle #2Taking out (Extraction)

3Productivity

If multiple filters are placed in series to maintain high permeate flow rate, then permeate flow rate increases, but system complexity increases

Engineering Contradiction:
Improvepermeate flow rateVSAvoidfiltration system configuration
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the filtration function across multiple filters connected in series, where each filter handles a portion of the total filtration load. This segmentation allows the system to maintain high permeate flow rates by distributing the flow across multiple filtration surfaces, effectively multiplying the total filtration capacity without requiring a single complex filter unit

Inventive Principle:
Principle #1Segmentation

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 solution achieves significantly higher permeate flow rates and minimizes manual intervention, increasing efficiency and yield while maintaining consistent product quality, with permeate flow rates more than doubling and tripling with two and three filters in series respectively, and reducing shear on the product.

Implementation Method 1

The circulating process stream permits the continuous filtration of the desired product using a tangential flow filtration system through at least one filter

Methodology Applied
Scientific EffectTangential flow filtration: Filter (physical)

Implementation Method 2

a back-flush flow of clean liquid through the filter to dislodge particles and to replace the volume of liquid lost as the permeate stream

Methodology Applied
Scientific EffectPermeation: Permeation

Implementation Method 3

a back-flush flow of clean liquid through the filter to dislodge particles and to replace the volume of liquid lost as the permeate stream

Methodology Applied
Scientific EffectBack-flush flow: Fluid Spray

Implementation Method 4

The self-contained process unit allows for a circulating stream of materials within the unit

Methodology Applied
Scientific EffectRecirculation: Convection

Data Source

PatentEP2300419B1Method and apparatus for preparing a solution of a shear sensitive material
Publication Date: 2015.07.15 OTSUKA AMERICA PHARMACEUTICAL INC
  • EP2300419B1 patent drawingFigure 1
  • EP2300419B1 patent drawingFigure 2
  • EP2300419B1 patent drawingFigure 3

AI summary

The invention provides a novel apparatus and method for preparing a solution of a shear sensitive material.