DRAFTINFLUENCE OF PHYSICS OF

TABLET COMPRESSION

Scale-upPresenter: Alberto Cuitino

November 3rd, 2010

DRAFTDesign Pharmaceutical Solids

-12-10 -8 -6 -4 -2 0 2 4

-1000-800-600-400-200

0200

Die Filling Compression Breakup DissolutionMixing

EXPERIMENTS

MODELING & SIMULATIONS

Integrated

Integrated

DRAFTLarge-Scale

• Mechanistic models are used to generate coarse-graining schemes (response surface) for scaled-up systems

• Response surface is utilized for selecting best mechanistic parameters

• Parameters are utilized for overall product level optimization

DRAFTKey modeling aspect for scale-up:

Bonding

DRAFT0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0 5 10 15 20 25 30

Separation

Forc

e

-8

-7

-6

-5

-4

-3

-2

-1

0

1

2

0 2 4 6 8 10 12 14 16 18 20

Separation

Forc

e an

d P

oten

tial

Modified Logistic Equation

21

311

1.011

301.01ln

1

1

dce

F

cdecdU

cd

cd

0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

Time

Bon

ding

Str

engt

h

σ A – contact area

Bonding Force

History-dependent strength

History-Dependent Bonding

DRAFTColor represents the

strongest bond a particle has with its

neighbors.

Young’s ModulusE=25GPa

Poisson Ratioν=0.3

Size RangeAvicel 101: 60±10μm - 50%Avicel 102 :110±10μm - 50%

History-Dependent Bonding

DRAFT-12 -10 -8 -6 -4 -2 0 2 4

-1000

-800

-600

-400

-200

0

200

Displacement

Pressure

Compressive Loading

Relaxation

Tensile Loading

Failure

Tablet Compaction and Tensile Loading

DRAFTTablet Compaction and Tensile Loading

DRAFTHere goes the connection with

the Abbott Data (Steve)

DRAFTConclusion