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1. APV-Forum Feuchtemesstechnik28.11. und 29.11.2006 Dresden

Online Moisture-Measurement in Fluidised-Bed –

Granulate- and Dryingprocess

Design of a Sensor to meet “pharma-requirements”including first expieriences in a

Glatt – Fluidised-Bed – Granulator

Dr.-Ing. Claas Döscher

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1994: Döscher & Döscher GmbHDistributor of Industrial Moisture-Measurement-Devices

2001: Foundation of AMS GmbH [Advanced Microwave Systems]

Development and Manufacturing ofMeasurement-Systems to verify Moisture-and Density by Microwave-TechnologyCo-operation with Prof. Knöchel, CAU

Company

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Project - Team

Prof. Dr. Jörg Breitkreutz:University of Düsseldorf

Caroline Buschmüller: University of Düsseldorf

Dr. Wolfgang Wiedey: Pharbil Waltrop GmbH

Dr. Jochen A. Dressler: Glatt GmbH

Dr. Claas Döscher: Döscher&Döscher GmbH

Mikrowave - Moisture - Measurement

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Physical Basics of Microwave-TechnologyMeasurement-PrincipleAdvantagesDesign of SensorMaterials of the TrialEquipmentResultsAdvantages for the Granulate-Process

Structure

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Physical Basics

WassermolekülTrägermaterial

Wasser im Produkt

Water Molecule

Water in Product

Carrier Material

Trägermaterial

WassermolekülWater Molecule

Carrier Material

Electro-Magnetic Field

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Two Measurement-Signals will be needed for measuring the Moisture.

Physical Basics

2-Parameter Microwave Resonance Principle

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Number of water-molecules is determined byMoisture and Density

same relative Moisture

low density high density

Physical Basics

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Energy-Carryover from field to product

Change of velocity of propagation

Physical Basics

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Electric-flux-lines of ascatter field sensor

Measurement-Principle

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Spectrum ofresonances ofvarious densities

Measurement-Principle

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Loss of energy andfrequency-shift ofvarious densities

Measurement-Principle

0 1 2 3 4

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Microwaves penetratematerial

Moisture will be measured on surface as well as in kernel

Advantages

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density-independent moisture-measurementno influence of any contaminationfast, ca. 1/500 secindependent from color and structuremeasures on surface as well as in kernellong-term and stable calibrationlarge independency from carrier material

Advantages

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Includes Reference-Resonator:

Design of Sensor

Patent EP 1331 476

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Conventionel Design Improved Design

Design of Sensor

Keramik

2 K Kleber

Keramik mitLeiterbahn

Edelstahl

Dielectrical Plastic Material includingCircuit Path

2-Component-Glue

Stainless Steel

Ceramic

Patent EP1437588

Titan

Keramikring

Titan

Ceramic Ring

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Requirements to the Measurement:

density-independentno influence of temperature-variationsdetects moisture on surface as well as in kernelindependent from structure of product(powder => granulate)ATEX 20 dust-explosion-protectionsensor-sidedpressure-resistant up to 15 barpharma-appropriate materials

The TaskContinuous Moisture Measurement in theFluidised-Bed-Process of a Pharmaceutical Production

low density high density

Streaming

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Materials of the Trial

Dehydration GlattMicrocrystal Cellulose 2 kgLactose 200 mesh 4 kg10 % Kollidon(R) 90F 1,7 kg

Granulation GlattMicrocrystal Cellulose 2 kgLactose 200 mesh 4 kg6 % Kollidon(R) 90F 10 kg

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Streaming GlattMicrocrystal Cellulose 2 kgLactose 200 mesh 4 kg6 % Kollidon(R) 90F 10 kg

Granulation Pharbil80 % Microcrystal Cellulose20 % Active IngredientGranulate-Liquid: watery Kollidon(R) Solution

Materials of the Trial

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PlantGPCG 15 (Glatt)WSG 60 (Glatt)MoistureScan (Döscher&Döscher)

ProcessesDehydration in Fluidised BedSpray Granulation in Fluidised Bed

CalibrationKarl Fischer TitrationLOD 70°C

Equipment

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Equipment

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Equipment

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Equipment

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Results

Trocknungskurve 27-09-II GPCG 15 (Glatt)

0

10

20

30

40

50

60

70

10:48 10:55 11:02 11:09 11:16 11:24 11:31

Zeit

Tem

pera

tur

0

2

4

6

8

10

12

14

proz

entu

ale

Feuc

hte

LOD

Dehydration-Diagram

rela

tive

Moi

stur

e

Tem

pera

ture

Time

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Results

Trocknungskurve 26-09-II GPCG 15 (Glatt)

0

10

20

30

40

50

60

70

14:52 15:00 15:07 15:14 15:21 15:28 15:36 15:43Datum und Uhrzeit

Prod

uktt

empe

ratu

r

-1

1

3

5

7

9

11

13

15

proz

entu

ale

Feuc

hte

LOD

Dehydration-Diagram

rela

tive

Moi

stur

e

Pro

duct

-Tem

pera

ture

Date and Time

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Results

Granulierungskurve 27-09- VI GPCG 15 (Glatt)

0

5

10

15

20

25

30

35

40

45

50

14:52 15:07 15:21 15:36 15:50 16:04 16:19 16:33

Uhrzeit

Prod

uktte

mpe

ratu

r

0

1

2

3

4

5

6

proz

entu

ale

Feuc

hte

LOD

Dehydration-Diagram

Time

Prod

uct-T

empe

ratu

re

rela

tive

Moi

stur

e

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Results

Granulierungskurve 27-09- V GPCG 15 (Glatt)

0

10

20

30

40

50

60

14:16 14:24 14:31 14:38 14:45

Uhrzeit

Prod

uktte

mpe

ratu

r

0

0,5

1

1,5

2

2,5

3

3,5

4

4,5

proz

entu

ale

Feuc

hte

Sprühluft ausgefallen -> Klumpenbildung

Time

rela

tive

Moi

stur

e

Prod

uct-T

empe

ratu

reGranulation-Diagram

Breakdown of Spraying Formation of Lump

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Results

variable Durchströmung (Glatt)

0

0,5

1

1,5

2

2,5

3

0:00:00 0:02:53 0:05:46 0:08:38 0:11:31 0:14:24

Zeit

proz

entu

ale

Feuc

hte 0 m³/h

500 m³/h1000 m³/h1500 m³/h1700 m³/hLOD 70 °C

Granulat wird leicht nachgetrocknetStarke Änderung der Fluidisierung -> keinen Einfluss auf die Messung

rela

tive

Moi

stur

e

Time

Streaming variable (Glatt)

Granulate slightly dehydratedStrong Variation of Fluidising

no Influence to Measurement

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Results 2006-07-21 Ansatz 2 (Granulierung Pharbil)

20

25

30

35

40

45

00:00 00:28 00:57 01:26 01:55Zeit[hh:mm]

Tem

pera

tur [

°C]

0,00

1,00

2,00

3,00

4,00

5,00

6,00

7,00

8,00

Feuc

hte

[%]

Moi

stur

e [%

]

Tem

pera

ture

[°C

]

2006-07-21 Make-Up 2 (Granulation Pharbil)

Time [hh:mm]

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Results

2006-07-21 Ansatz 2 (Granulierung Pharbil)

20

25

30

35

40

45

00:00 00:28 00:57 01:26 01:55

Zeit[hh:mm]

Tem

pera

tur [

°C]

0,00

1,00

2,00

3,00

4,00

5,00

6,00

7,00

8,00

Feuc

hte

[%]

Karl Fischer

2006-07-21 Make-Up 2 (Granulation Pharbil)

Moi

stur

e [%

]

Tem

pera

ture

[°C

]

Time [hh:mm]

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Results

Korrelation (Granulierung Pharbil)

R2 = 0,9696

3,50

4,00

4,50

5,00

5,50

6,00

6,50

7,00

7,50

3,50 4,00 4,50 5,00 5,50 6,00 6,50 7,00 7,50

Karl-Fischer Messung

kalib

r. M

ikro

wel

lenm

essu

ng

Messungen 07-2006 Messungen 09-2006

Correlation (Granulation Pharbil)

Cal

ibra

ted

Mic

row

ave-

Mea

sure

men

t

Karl-Fischer Measurement

Meas. 07-2006 Meas. 07-2006

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Aim:Prevention of Over-DehydrationPelleting: Tablets partly are flakingPrevention of Under-DehydrationPelleting: Granulate or Powder is gluing onto Punching Tool

Accurate achieve to the target-moisturePrevention of repeated make-up of Dehydration-Process, Quality of Granulate

Reproducable target-moistureeven when climate is changing when drying with ambient air.Proper Validation of Process

Information about Homogenity of Product

Advantages for the Granulate-Process whenVerifying Moisture

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Time saving due to Online-Validation of the Process

Automated Control of air-supply-temperature to aim for a constant of dehydration-rateGentle dehydration possible

Control of Product-Moisture to optimisinggranulate, grading is starting with product-specific, ideal moistures

Advantages for the Granulate-Process when Verifying Moisture