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Granulation - a process with many faces

WIM OOSTRA

25| October | 16

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CONTENT

• Introduction

• Mechanisms of granulation

• Nucleation and wetting

• Growth and coalescence

• Breakage and attrition

• Outlook

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WHY GRANULATION

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The Science and Engineering of Granulation ProcessesBy Jim Litster, Bryan Ennis

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HOW

Dry

• Roller compaction

• Tablet compaction

• Pelletizing mills

Wet

• Drum granulators

• Disc granulators

• Planetary mixers

• High shear mixers

• Fluid bed granulators

• Extruders

• Spray drying

• Prilling

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PHARMA

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- FUTURE?

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MECHANISMS IN GRANULATION

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NUCLEATION AND WETTING

“Pour on”

• Relies on mechanical dispersion

• Short nucleation times

• Can be very reproducible for low viscous binders

Spray-on

• Use spray flux density

• Well controlled nucleation

• Lead to long nucleation times in scale up and wider distributions

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𝜓𝑎= 3 𝑉

2 𝐴𝑑𝑑

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NUCLEATION AND WETTING

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Nucleation regime maps

K.P. Hapgood, J.D. Litster, R. Smith, AIChE L, 49 (2), 350-361, 2003

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NUCLEATION AND WETTING - EXAMPLE

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5003: Penetration time of binder > 60 s5004: Penetration time of binder < 1 s

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NUCLEATION AND WETTING – EXAMPLE 2

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MECHANISMS IN GRANULATION

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CONSOLIDATION AND COALESCENCE

• Growth (pattern) observed depends on

• Strength/deformability of granules (particle size, viscosity, porosity)

• Pore saturation

• Force applied (Fluid bed vs. high shear, impeller/chopper speeds )

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CONSOLIDATION AND COALESCENCE

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CONSOLIDATION AND COALESCENCE

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Granule growth regime map

S.M. Iveson and J.D. Litster, AIChE J 44, 1510-1518 (1998)

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CONSOLIDATION AND COALESCENCE

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Layered growth

Layered growth

K. Van den Dries, Paradox of high shear granulation, PhD thesis, Utrecht, 2004

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MECHANISMS IN GRANULATION

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ATTRITION AND BREAKAGE

• Important process which affects, even, may control the PSD….

• Less understood than other phenomena

• Difficult to study/separate from other phenomena

• Various semi-quantitative theories available

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BREAKAGE

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ATTRITION AND BREAKAGE

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0.0000 0.0001 0.0010 0.0100 0.1000 1.0000 10.0000

StdefGral 10

Gral 25

Gral 75

Gral 300

Breakage

No breakage

No breakage Breakage

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MECHANISMS IN GRANULATION

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SUMMARY, OUTLOOK

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