Improving the prediction of multicomponent tablet properties from pure component parameters Hikaru G. Jolliffe, Foteini Papathanasiou, Elke Prasad, Gavin Halbert, John Robertson, Cameron J. Brown, and Alastair J. Florence. Formative Formulation meeting Maxwell Centre, Cambridge. 18 th March 2019
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Improving the prediction of multicomponent tablet properties from pure component parameters
Hikaru G. Jolliffe, Foteini Papathanasiou, Elke Prasad, Gavin Halbert, John Robertson, Cameron J. Brown, and Alastair J. Florence.
Formative Formulation meetingMaxwell Centre, Cambridge.
18th March 2019
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 2
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
1. Introduction
2. Compression model
3. Experimental work
4. Parameter estimation and predictive model
5. Conclusions
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 3
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Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 4
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 5
TKTT P1*0
* rr =
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
Compression modelGavi and Reynolds (2014) model
Tablet relative density ("#∗ ): power law• Variables: compression pressure (P)• Parameter: tablet relative density at zero P ("#%∗ )• Fitted parameter: compressibility constant (&#)
Mixing rules for multicomponent tablets:• kb and '#% - gPROMS implemented (volume fraction-based)• &# - user-specified (also volume fraction-based)
ess bkTT e-= 0
TT
compT hd
Fp
s 2=
ii
iTmixT fss å= ,0,0 ii
ibmixb kk få= ,, ii
iTmixT KK få= ,,
SU
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 6
Introduction gPROMS and compression model Experimental workParameter estimation and predictive
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 7
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 8
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 9
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
Key compression data for Avicel PH-101 tablets (200 mg target mass)
Compression force
(kN)
Tablet mass
(mg)
Tablet thickness
(mm)
Tablet hardness
(N)
0.76 197.32 4.647 16.9
1.97 197.44 3.481 63.4
4.01 198.72 2.850 140.6
6.04 197.79 2.562 206.4
8.04 199.05 2.531 254.0
9.70 197.13 2.450 291.4
11.68 197.37 2.265 326.1
13.90 196.81 2.224 351.8
14.96 197.47 2.216 366.8
16.57 197.72 2.168 374.7
17.70 197.34 2.177 390.0
18.95 197.32 2.186 396.6
0
100
200
300
400
500
600
0 5 10 15 20
Tabl
et h
ardn
ess
(N)
Compaction force (kN)
200 mg (experimental)
200 mg (predicted)
250 mg (experimental)
250 mg (predicted)
Optimal pure component parameters for Avicel PH-101 and Pharmatose 50M.
Parameter estimation: results for pure cellulose and lactose tablets
0
1
2
3
4
5
6
7
0 5 10 15 20
Tabl
et th
ickn
ess
(mm
)
Compaction force (kN)
200 mg (experimental)
200 mg (predicted)
250 mg (experimental)
250 mg (predicted)
Pharmatose 50M (lactose)
Avicel PH-101 (cellulose)
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 10
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
0
50
100
150
200
250
300
0 2 4 6 8 10 12 14 16 18 20
Tabl
et h
ardn
ess
(N)
Compression force (kN)
99% CIMeasuredPredicted
0
50
100
150
200
250
300
0 2 4 6 8 10 12 14 16 18 20
Tabl
et h
ardn
ess
(N)
Compression force (kN)
0
50
100
150
200
250
300
0 2 4 6 8 10 12 14 16 18 20
Tabl
et h
ardn
ess
(N)
Compression force (kN)
0.0
1.0
2.0
3.0
4.0
5.0
0 2 4 6 8 10 12 14 16 18 20
Tabl
et t
hickn
ess
(mm
)
Compression force (kN)
99% CIMeasuredPredicted
0.0
1.0
2.0
3.0
4.0
5.0
6.0
0 2 4 6 8 10 12 14 16 18 20
Tabl
et t
hickn
ess
(mm
)
Compression force (kN)
0.0
1.0
2.0
3.0
4.0
5.0
0 2 4 6 8 10 12 14 16 18 20Ta
blet
thic
knes
s (m
m)
Compression force (kN)
50-50 Lact-Cel 60-40 Lact-Cel 70-30 Lact-Cel
Parameter estimation: results for binary cellulose and lactose tablets
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 11
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
Parameter estimation: results for binary cellulose and lactose tablets
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 12
0
50
100
150
200
250
P T T*
Volume
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 13
0
1
2
3
4
5
6
0
50
100
150
200
250
300
350
400
0 5 10 15 20 25 30Ta
blet
thic
knes
s (m
m)
Tabl
et h
ardn
ess (
N)
Compaction force (kN)
0
1
2
3
4
5
6
0
50
100
150
200
250
300
350
400
0 5 10 15 20 25 30
Tabl
et th
ickn
ess (
mm
)
Tabl
et h
ardn
ess (
N)Compaction force (kN)
Hardness (Gavi and Reynolds, 2014)
Hardness (MATLAB)
Hardness (measured)
Thickness (Gavi and Reynolds, 2014)
Thickness (MATLAB)
Thickness (measured)
0
1
2
3
4
5
6
0
50
100
150
200
250
300
350
400
0 5 10 15 20 25 30
Tabl
et th
ickn
ess (
mm
)
Tabl
et h
ardn
ess (
N)Compaction force (kN)
0
1
2
3
4
5
6
0
50
100
150
200
250
300
350
400
0 5 10 15 20 25 30
Tabl
et th
ickn
ess (
mm
)
Tabl
et h
ardn
ess (
N)
Compaction force (kN)
50-50Lactose-Cellulose
60-40Lactose-Cellulose
1
2
3
4
5
6
0 5 10 15 20 25
Dist
ance
(mm
)
Compaciton force (kN)
Punch gapTablet thicknessPunch gap (measured)Thickness (measured)
PH-101 200 mg, punch gap and tablet thickness
y = 46.90666x-0.31744
R² = 0.99829
10
15
20
25
0 50 100 150 200 250 300 350
Mas
s-to
-gap
fact
or γ,
mm
/g
Compaction pressure (MPa)
200 mg tablets
225 mg tablets
250 mg tablets
ε = l imit
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
PH-101, punch gap and compaction pressure
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 14
KEY DATAIndependent
ForceMass
Punch gap
DependentHardnessThickness
PURE COMPONENT PARAMETERS
σ0ikbiKTiAibini
Mixing rules +Compression
model
BINARY / TERNARYTABLET
PROPERTIES
σtabhtabεtab
gPROMS
MATLAB
gPROMS
Excel
OPTIMISATIONMATLAB
Tablet_optimiser.exe
PACKAGE INTO APP
Optimal experimental
settings
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 15
Introduction gPROMS and compression model Experimental work Parameter estimation and predictivemodel Conclusions
Extensive compression data generated for a variety of materials and material grades
Optimal values for key parameters (!", kb, #"$) found• For pure components• Good fits to experimental data
Binary tablet properties predicted using pure parameters• Various tablet compositions• Predictions improved with modified parameter weighting.
Ongoing work• More components, additional validation• Lubrication effects
Conclusions & Final Remarks
SU
Improving the prediction of multi-component tablet properties from pure component parametersH.G. Jolliffe – Formative Formulation meeting, 18 Mar 2019, Maxwell Centre, Cambridge, UK 16
This work was supported by:
University of Strathclyde• Foteini (Fay) Papathanasiou, MSc• The authors would like to acknowledge that this work was carried out in the CMAC National Facility
supported by UKRPIF (UK Research Partnership Fund) award from the Higher Education Funding Council for England (HEFCE) (Grant ref HH13054)