Online Tablet Coating Thickness sensor for

a Perforated Pan Coater

Dipankar Dey
Head of Process and Validation
OYSTAR Manesty

OYSTAR Manesty PAT Technology Development:

Online coating thickness sensor

Developed in response to FDA PAT Initiative on Process Understanding

Collaboration funded by UK Government Technology Strategy Board
Partners: TeraView Ltd, University of Cambridge, University of Liverpool

Manesty PAT Technology | Dipankar Dey | 110510

OYSTAR Manesty PAT Technology Development

Motivation: Modified Release tablet manufacturing

Consortium Approach
Results
Applications
Project Offerings

Manesty PAT Technology | Dipankar Dey | 110510

Motivation: Issues in manufacture of

Modified Release Tablets

Many new drugs have modified release characteristics

Modified Release product market size is growing
2007= $65 billion
2010=$100 billion
Will grow further as existing product patents expire and
manufacturers introduce line extensions of existing products
.
AVANDIA

AVANDAMET

Manesty PAT Technology | Dipankar Dey | 110510

AVANDARYL

Motivation: Issues in manufacture of

Modified Release Tablets

Complex products manufacturing challenge

High failure rates
10-25% manufactured batches wasted (industry sources)
Urgent need for non-destructive analysis of tablet coatings
Multi-layer analysis
Coat quality

Manesty PAT Technology | Dipankar Dey | 110510

Consortium approach: Use of THz

Spectroscopy for online layer thickness
measurement

THz imaging already proven offline for direct measurement of

multilayer tablet coatings as found in Modified Release products

THz is the only spectroscopic method that gives statistical data on

a large number of individual tablets during a run rather than an
average value, giving important distribution data

The results from the terahertz coating analysis can be directly

correlated to the drug release of the coated tablet*
* Ho et al., J. Contr. Rel. 127, 79-87 (2008)

Manesty PAT Technology | Dipankar Dey | 110510

Terahertz Pulsed Imaging (TPI)

Terahertz radiation (2 cm-1 120 cm-1)

Single
incident
THz pulse

Penetrates through most pharmaceutical

excipients
Novel technique for non-destructive tablet
coating quality analysis
THz Imaging
Pulse echo measure thickness of tablet
layers.
Single tablet is held stationary in well
defined orientation.
Layers determined by change in RI.
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multiple
return pulses

Coated
tablet

Comparison with NIR & OCT

TPI

NIR

OCT

Spectralrange

1000100microns

2.550.9microns

1.10.5microns

Penetrationdepth

1000smicrons

10smicrons

10smicrons

Depthresolution

40micronsorbetter

10microns

Submicron

Depthprecision

2microns

Afewmicrons

Submicron

Measurementtime

20ms(ableto
resolvetablettablet
variationwithina
batchinrealtime)

30secondswitha
cooledCCD(msif
usinghighpower
lightsource)

40seconds(msif
usinghighpower
lasersource)

Colorsensitive?

No

No(yes)

Yes(no)

Directmethod?

Yes,selfreference

No(calibration
modelrequired)

Yes,selfreference
(processedsignal)

Manesty PAT Technology | Dipankar Dey | 110510

IMAGA 2000 Coating Thickness

Measurements Offline using Robotic
Analyser

Variation in a laboratory scale batch

in ten sustained release products
10% variation
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Data from whole surface:

Hardness
Layer thickness
Layer integrity
Layer uniformity

The Online Measurement Concept

Emitter

Receiver

Challenge: to measure the coating thickness

of large numbers of randomly moving tablets
in a coating drum
THz

Current techniques are extremely well

controlled

Superficially tablets in random motion in a

coater

Tablets actually arrayed against drum mesh

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Moving
tablet bed

Tablet alignment with drum

With larger numbers

Align against a linear

array of tablets

Apply strict selection

criteria

A statistical approach
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drum movement

there is a finite
probability that a tablet
will arrive with the
correct position and
orientation to be
measured. Only those
tablets will produce
strong reflected signals

Sensor Head Design

Single body
Electronics in Head (reduced losses)
Hermetic
Interchangeable optics
CIP compatible
Umbilical multi positional for flexibility

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Patented Sensor Positioning

Sprung roller mount concept

Enhanced hit rate
Rigid mounting position
Enhanced stability
Retrofit option

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Principle of THz Online Measurement

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The Key to the Technology

Waveform Selection
Only tablets normal to the THz beam
Acceptance based upon
Position
Amplitude
Shape
Self-referencing
Reflections from drum surface
Direct measurement
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In line results-10mm tablets coated to 10%

weight gain with an enteric coating

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Tablet Coat Thickness Distribution with time

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Time (H)

No of
tablets

Mean
Thickness
(um)

SD

982

55

23

755

92

20

655

105

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Histogram of tablet distributioncomparison with off line measurement

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Tablet Distribution Implications

Wide range of tablet coat

thickness
41 to 111 microns
623 tablets measured

Important to understand
extremes of distribution

Online NIR only gives average

with no details of this
distribution

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Off spec product?

Statistical distributions provided by THz Sensor

Average thickness

Number of tablets

Off spec FDA issues, wasted

material, extra testing, failed
dissolution = Cost

Batch 1
Poor
uniformity

Batch 2
improved
uniformity

Coating thickness

THz allows distribution information to ensure stable and In spec product

Both batches have the same average NIR would report both as the same
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Applications: Early warning sensor for coating quality

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Orange Peeling

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Picking

Identification of Coating Defects:

Sudden increase in Standard

Deviation would indicate that the
surface finish of the tablet is
incorrect and that Orange
Peeling is occurring
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Unexpectedly low coating

thickness readings would indicate
that the coating is delaminating
and that Picking is occurring

When and how would this technology add value?

Faster Product Design

Helping to quickly measure properties that can then be
correlated to performance

Faster Process Development

On-line monitoring allows the rapid optimisation of process
conditions to ensure the correct thickness and optimum
distribution

Safer and Quicker Technology Transfer

Direct measurement of quality critical properties at the sender
and receiver

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When and how would this technology add value?

Cost Reduction
Optimum amount of coatings
Lower batch failures + quicker problem detection
Avoid wastage from in process sampling
HSE
Reduced in process sampling reduces operator exposure and
waste

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Stepwise/ Project based approach

We can provide project services for the design and process optimisation
of the tablet coating process
Off line we can study
Coating uniformity
Coating variability tablet to tablet
How coating thickness varies with different time points
How all of the above affect dissolution

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Stepwise/ Project based approach

The Online system can monitor performance in real time and allows rapid
optimisation of Manesty coater system. This can be done at Manesty or
on site (subject to coater configuration).
Site installation of the Online system will be with full application support
from Teraview and OYSTAR Manesty

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Summary

Tablet coating in a pan will produce a tablet to

tablet distribution of thickness
This distribution needs to be understood and
controlled to ensure batch quality

THz Pulsed Imaging is the only online technique

that can measure distribution
Alternative techniques only look at averages

This project has demonstrated at scale that

we can monitor thickness and the
distribution of thickness within a coating pan.

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Summary

This technology can

Speed Product Design
Speed Process Development
Enable efficient Technology Transfer
Reduce material costs and product failures
Improve HSE of operations
OYSTAR Manesty and TeraView can offer
services, equipment and technical support to
make this happen

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The Complete Tableting Compression and Tablet Coating Solution

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OYSTAR Manesty
Kitling Road Knowsley
Merseyside England L34 9JS
T +44 (0)151 547 8000 F +44 (0) 151 547 8001
Info@oystar.manesty.com www.oystar.manesty.com

Validation of coating thickness distribution

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In line results
Enteric coating of 10mm tablets

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