ChemicalEngineering3

Par0clesizeenlargement(Agglomera0on)

Powder

Pellets

Tablets

Granules

Agglomeration = particle size enlargement

1) Purpose: - improve flow properties - improve dispersion/dissolution properties - ensure composition uniformity (segregation) - reduce dustiness - improve visual appeal - dosage uniformity

2) Mechanisms: - “Dry” agglomeration (compaction) - “Wet” agglomeration

3) Equipment

4) Population balance model

Mechanical agglomeration

(tabletting, roll compaction, pelletisation, briquetting…)

Elastic deformation

Plastic deformation

Brittle failure

before after during

Single particle

Force

Phenomena: - Particle rearrangement - Elastic deformation - Plastic deformation and/or viscous flow - Particle bonding (adhesion bonding, diffusion bonding) - Brittle failure - Elastic recovery

Strain (Δx/x0)

Stress (Force/Area)

Heckel model (1st order):

ln(1/1-D)=P/Py+A

D… relative density ρ/ρ0 P… applied pressure A… particle rearrangement Py… yield pressure (material property)

Low Py … soft/plastic materials (5-50 MPa) High Py … hard/brittle materials (100-1000 MPa)

Roll compaction

Tabletting

Cyclic operation:

-  Feed

-  Pre-compact

-  De-aerate

-  Final compaction

-  Eject

Need to use lubricants (e.g. magnesium stearate) to avoid sticking to punch or die walls and reduce wear.

Problems: capping, de-lamination

Tablet press

Wet granulation: principle

Wet Granulation

Principle: contact powder with a liquid binder, wet powder particles become cohesive, agglomeration occurs during particle collisions, binder sets to form mechanically stable granules.

Binder types: -  melt binders ~ melts, solidify upon cooling (e.g. PEG) -  aqueous binders ~ solutions, solidify upon drying (e.g. PVP) -  water ~ partial dissolution and recrystallisation of ingredient(s)

Binder application: -  spray (liquid atomisation) for low-shear processes -  mechanical dispersion in high-shear processes

Granulation processes: -  fluid bed granulation -  high-shear mixer granulation

Fluid bed granulation - batch

Top spray Bottom spray (Wurster)

Fluid bed granulation - continuous

Fluid bed granulation - continuous

https://www.youtube.com/watch?v=CICJGx0QNPs

Drum granulator

Large scale: minerals, iron ore, fertilisers…

Pan granulator

Mechanically agitated granulators - continuous

Single-shaft (plough shear)

Twin-shaft (paddle mixers)

Batch high-shear mixer-granulator

Growth regime map (Iveson & Litster, AIChE J 44, 1510, 1998)

€

Stdef =ρgUc

2

2Yg

€

smax =wρs(1− εmin )

ρlεmin

Liquid distribution in a wet granule:

Image © Ullmann’s Encyclopedia of Industrial Chemistry

A)  pendular

B)  funicular

C)  capillary

D) droplet

Extrusion-spheronisation

Principle of operation: - Prepare a paste from API, excipients, binder, water - Extrude paste through screen to form “noodles” - Contact extrudates with a high-speed rotating disk - Dry resulting spherical pellets

…but it is also possible to carry out spheronisation after wet granulation

Population balance of agglomeration

ck … volumetric concentration of granules consisting of k primary particles (single granule mass mk= km1)

€

dckdt

=12

βijcic j −i=1, j=k− i

k−1

∑ βikcicki=1

N

∑ +1τ(ck

in − ck )

βij .. agglomeration kernel (rate constant)

€

βij = β0ψ ijgeomψ ij

phys β0 ... collision frequency

Ψij ... success factors

si ... surface coverage

€

ψ ijgeom =1− (1− si)(1− s j )

Conditions for agglomeration of wet patricles

Criteria for coating vs. agglomeration:

⎟⎟⎠

⎞⎜⎜⎝

⎛=≤=

avv h

StDumSt λ

πµln2~3

~8 *20

: viscous Stokes number : reduced particle mass : reduced particle diameter : velocity of collision

: binder viscosity : thickness of binder layer : particle surface roughness

vStm~

D~

0u

µ

λ

ah

Complete granulation plant with recycle