Tabletability, compactibility and compressibility: a complex relationship easily displayed with JMP.

Tabletability, compactibility and compressibility: a complex relationship easily displayed with JMP.

Diletta Biagi – Università di Firenze Paolo Nencioni – Manufacturing Science and Technology, A.Menarini M.L. & S.

Summary

• Tablets and powder compression • Compaction studies • Data modelling • Data visualization • Real case studies

Tablets are the most popular drug delivery dosage form

Density

Applied Force (kN)

Shape area

Thickness

Volume

Weight

Hardness

Powder Tablets

Particle Size

Particle Shape

Flowability

Compression

Applied Force (kN)

Compaction Pressure

𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒 =𝐴𝑝𝑝𝑙𝑖𝑒𝑑 𝐹𝑜𝑟𝑐𝑒

𝐴𝑟𝑒𝑎

Tensile Strength

𝑇𝑠 =2 ∙ 𝐹

𝜋𝐷𝑇

True Density

The powder density once all voids are removed.

Solid Fraction

𝑆𝑜𝑙𝑖𝑑 𝐹𝑟𝑎𝑐𝑡𝑖𝑜𝑛 =𝑇𝑎𝑏𝑙𝑒𝑡 𝐷𝑒𝑛𝑠𝑖𝑡𝑦

𝑇𝑟𝑢𝑒 𝐷𝑒𝑛𝑠𝑖𝑡𝑦

𝑃𝑜𝑟𝑜𝑠𝑖𝑡𝑦 = 1 − 𝑆𝑜𝑙𝑖𝑑 𝐹𝑟𝑎𝑐𝑡𝑖𝑜𝑛

0

5

10

15

0 100 200 300 400 Compaction Pressure (MPa)

Compaction Studies

0,6

0,7

0,8

0,9

1,0

0 100 200 300 400 Compaction Pressure (MPa)

0

5

10

15

0,7 0,8 0,9 1,0 Solid Fraction

Tabletability profile Compressibility profile Compactibility profile

Ten

sile

Str

en

gth

(M

Pa)

So

lid

Fra

ctio

n

Ten

sile

Str

en

gth

(M

Pa)

Tensile strength by

Compaction pressure

Solid fraction by

Compaction pressure

Tensile strength by

Solid fraction

Flat-face punch 11,89 mm – Area 1 cm2

True Density Estimation

𝑃 =1

𝐶1 − 𝜀𝑐 −

𝜌𝑡𝑎𝑏𝑙𝑒𝑡

𝜌𝑡𝑟𝑢𝑒− 𝜀𝑐 ln

1 −𝜌𝑡𝑎𝑏𝑙𝑒𝑡𝜌𝑡𝑟𝑢𝑒

𝜀𝑐

Heckel equation

Non linear model library

C. Sun, A Novel Method for Deriving True Density of Pharmaceutical Solids Including Hydrates and Water-Containing Powders, (2013)

where:

tablet is the variable X

true is the parameter d

C, b and d are parameters

Analyze>Specialized Modeling>Nonlinear

True Density Estimation

𝑃 =1

𝐶1 − 𝜀𝑐 −

𝜌𝑡𝑎𝑏𝑙𝑒𝑡

𝜌𝑡𝑟𝑢𝑒− 𝜀𝑐 ln

1 −𝜌𝑡𝑎𝑏𝑙𝑒𝑡𝜌𝑡𝑟𝑢𝑒

𝜀𝑐

Heckel equation

Non linear model library

C. Sun, A Novel Method for Deriving True Density of Pharmaceutical Solids Including Hydrates and Water-Containing Powders, (2013)

where:

tablet is the variable X

true is the parameter d

C, b and d are parameters

Analyze>Specialized Modeling>Nonlinear

Compressibility Kawakita, Tsutsumi, A Comparison of Equations for Powder Compression, (1966) Physical Properties and Compact Analysis of Commonly Used Yeli Zhang, Yuet Law, and Sibu Chakrabarti, Direct Compression Binders, 2003

𝑃

𝐶=

𝑃

𝑎+

1

𝑎𝑏

Kawakita equation

Non linear model library

where:

P is the variable X

a and b are parameters

Analyze>Specialized Modeling>Nonlinear

𝐶 =𝑉0 − 𝑉

𝑉0

V0 starting vol. V vol. at applied pressure

𝐶 =𝑆𝐹0 − 𝑆𝐹

𝑆𝐹0

SF0 starting solid fraction V solid fraction at applied pressure

or

SF is the variable Y

Compressibility Kawakita, Tsutsumi, A Comparison of Equations for Powder Compression, (1966) Physical Properties and Compact Analysis of Commonly Used Yeli Zhang, Yuet Law, and Sibu Chakrabarti, Direct Compression Binders, 2003

𝑃

𝐶=

𝑃

𝑎+

1

𝑎𝑏

Kawakita equation

Non linear model library

Analyze>Specialized Modeling>Nonlinear

𝐶 =𝑉0 − 𝑉

𝑉0

V0 starting vol. V vol. at applied pressure

𝐶 =𝑆𝐹0 − 𝑆𝐹

𝑆𝐹0

SF0 starting solid fraction V solid fraction at applied pressure

or

Compressibility

The ability of a material to reduce in volume as results of an applied pressure

Compactibility C. K. Tye, C. Sun, G. E. Amidon, Evaluation of the Effects of Tableting Speed on the Relationships between Compaction Pressure, Tablet Tensile Strength, and Tablet Solid Fraction, (2005)

𝑇𝑒𝑛𝑠𝑖𝑙𝑒𝑆𝑡𝑟𝑒𝑛𝑔𝑡ℎ = 𝜎0𝑒−𝑏 1−𝑆𝑜𝑙𝑖𝑑𝐹𝑟𝑎𝑐𝑡𝑖𝑜𝑛

Fit Y by X platform

Simply doing a “Fit special” with Y transformed as logarithm

Ryshkewitch equation

Compactibility

The ability to produce tablets with sufficient strength, under the effect of densification

Tabletability

The capacity of a powder to be transformed into a tablet of specified strength under the effect of compaction pressure

Dashboard

3D Scatterplot

Compaction studies on cellulose, lactose and

placebo formulations

Lact

ose

C

ellu

lose

Cel

lulo

se 2

5%

La

cto

se 7

5%

C

ellu

lose

75

%

Lact

ose

25

%

Compaction studies on real tablets formulation,

using manufacturing punches (EU standard tooling)

Single punch press Vs Rotary press

Natoli NP-RD10A Single punch Alternative

Korsch PH103 Rotary press

Dwell time is defined as the amount of time that the compression force applied when forming the tablet is above 90% of its peak value.

Higher speed, shorter dwell time

Lower speed, longer dwell time

C. K. Tye, C. Sun, G. E. Amidon, Evaluation of the Effects of Tableting Speed on the Relationships between Compaction Pressure, Tablet Tensile Strength, and Tablet Solid Fraction, (2005)

Thank you References: • C.Sun, A Novel Method for Deriving True Density of Pharmaceutical Solids Including Hydrates and Water-Containing Powders, Journal of Pharmaceutical Science,

(2013) • Kawakita, Tsutsumi, A Comparison of Equations for Powder Compression, Bulletin of Chemical Society of Japan, (1966) • Y. Zhang, Y. Law, S. Chakrabarti, Physical Properties and Compact Analysis of Commonly Used Direct Compression Binders, AAPS PharmSciTech, (2003) • C. K. Tye, C. Sun, G. E. Amidon, Evaluation of the Effects of Tableting Speed on the Relationships between Compaction Pressure, Tablet Tensile Strength, and Tablet

Solid Fraction, Journal of Pharmaceutical Science, (2005) • C. Sun, Decoding Powder Tabletability: Roles of Particle Adhesion and Plasticity, Journal of Adhesion Sicence and Technology, (2011) • Natoli engineering, Tabletability, Compactibility, and Compressibility: What’s the Difference? , (2017)