Recent advances in the assessment of powder properties for

mixing and compression

Michael Gamlen

Gamlen Tableting Ltd

APS 2012

Important information

Tablets are, and will remain, the dominant pharmaceutical dosage form

Most tableting research was done in the 1980s and 1990s

Most tableting research has not been publishedor has been forgotten

Conclusion:By and large, we don’t know what we are doing!

Critical Quality Attributes of a compression mixture

Compressibility

Lubricity (acceptable level of lubrication)

Absence of capping

How many of these parameters are routines tested as IPCs?

Tablet machine operation

Die filling

Upper

Compression

Compression

Tablet detachment

Return to start

What can we measure during the compaction process?

Die filling

UpperWeight and weight

uniformity

Compression

Upper punch force

Lower punch force

Tablet thickness

Transmsittedforce

Tablet density

(needs tablet weight)

Punch position

Force/displacemement

profile

Compaction pressure

Ejection

Ejectionforce

Punch position

Ejection force/displacement

profile

Die wall pressure

Tablet detachment

Tabletdetachment

force

Return to start

Machine direction

Compression using a rotary tablet machine

FillDie

Adjust Weight

Compress Tablet

EjectTablet

Historical perspective (1)

First single punch tablet machine instrumentation publication

o 1951; Brake PhD ThesisPurdue University

Compaction force (upper and lower)

Ejection force

Historical perspective (2)

First rotary tablet machine instrumentation?early 1960s – Ridgway (SOP), Upjohn (USA)

First “accurate” measurement of displacement on single punch machine

1973, de Blaey

First truly accurate measurement of displacement on single punch machine

Ho, 1986

First published measurement of punch displacement on arotary tablet press

1990s, using telemetric systems but still extremely difficult to do

Historical perspective (3)

First machine to “simulate” compactiono Late 1970s – Wellcome, Glaxo, Pfizer etc

Publications from mid 1980s onwards

First tablet machine to actually check that measurements were correct

Developed 1978-1981by Peter Ridgway Watt (BeechamsPharmaceuticals) with Harry Seager and Peter Rue (latterly Glaxo)

Used instrumentation gauge slip-rings and modified pressure rollers

Compared output of strain gauged (moving) punches and LVDTs,with static transducers on tablet press

Not published except in highly abridged format

Watts Seager Rue (WSR) Press

In no case did forces recorded from any static location accurately record press parameters

o Precompression

o Compression (upper or lower)

o Ejection

For all measurements, the machine had to be extensively modified to get accurate data

o Extensive hysteresis and complete lack of accuracy and reproducibility

Measuring powder compressibility

Make a tablet and see how hard it is!

Tensile testing of tablets

UNIFORM STRESS ACROSS TABLET = RELIABLE TEST RESULT

Characterising tablet manufacture

Key types of measurement

1. During compaction process itself

2. After compressiona) “Direct” properties - weight, thickness

b) “Derived” properties – breaking strength, friability, disintegration, dissolution etc

Only measurements made during compaction process can be used to directly control the process, all others are “at line” or “off line” measurements.

Measurements made during compression“Compaction analysis”

Measurements made during compaction

Force (upper and lower punch)

Position (ditto)

Ejection

These give rise to derived parameters

Force/displacement

Compaction equations (Heckel, Kawakita etc)

Force

Fell and Newton, 1968