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Pharma Times - Vol 41 - No. 11 - November 200938
Untold millions of medicinal tablets and
capsules are produced every year, and manyof the over-the-counter varieties are encased
in blister packs for protection. Existing
manual methods for inspecting thesepackages are subjective and lack
repeatability, while electronic techniques
have to date been stymied by the greatvariation in blister packages. In both of these
cases, vision alone is not sufficient to meet
the QC needs of pharmaceutical packaging,whether that vision is human or machine. To
fill the gap, many technologies have been
developed to produce a nondestructive testmachine. Generalized statements often
made, such as no detectable leaks or leak
rate zero, no more represent an adequatebasis for acceptance tests. Sealing must be
quantified with an upper limit of an
admissible leak rate. Experienced engineers
know that properly formulated acceptancespecifications will indicate a certain leak rate
under defined conditions. Which leak rate is
acceptable can be determined by theapplication itself.
Current Trends In Blister Integrity Testing And NewDimensions To Blister Economies
Article
corresponding range of equipment. It is
necessary to choose a leak detection
method, which fulfills the defined needs ofsensitivity and speed; the chosen method
should not be more complicated and
expensive than necessary.
Challenging Application
Blister packs are considered aparticularly challenging application for leak
testing due to the following characteristics:
Flexibility of the package
Multiple cavities in one package
Small air volume inside each cavity
Relatively high production output on
automated packaging lines
Flexibility of automated packaging lines
resulting in frequent changeovers
Various materials used
Expensive product packed in a relativelyinexpensive container
Highly regulated industry.
Package Integrity Common
Misconceptions: If you dont see a leak, it isnt leaking
If you validate all packages and lines,
you wont have leakage problems
If you validate packages during R&D
using dye or microbial ingress, no
additional package integrity work willever be needed
Why Recalls Occur
Lack of sufficient inspection
Lack of process monitoring, process
control
Use of unreliable subjective techniques
(manual, visual)
Lack of proper process validation
Poor component quality
Inadequate maintenance
The Bottom line
Package integrity testing has neverbeen more critical than it is today.
The public has never been so informed
of package recalls as it is today.
What have been acceptable qualitystandards are now more stringent.
To protect the brand and maintainconsumer confidence.
Cost of insufficient package integritytesting
Recalls
Tracking and retrieving product,assessment
Fines and legal fees
Front page headlines
Loss of customer loyalty
Regulatory probation
Every corner cut in packaging qualitycontrol, opens the door for potential recalls
due to poor seal integrity.
Inspection Methods
Assess specific needs to verify packagequality
Ensure package maintains integrity until
product is used Determine how, when and why
packages fail
Evaluate inspection method andpotential results
Determine how results correlate topackaging process
Quality control / process control
Ideal test method:
The ideal blister package leak testingsystems do exist. The leak tester can, andshould, meet the following criteria:
Non-destructive and non-invasive
No sample preparation
Fast test time
Conform to regulatory requirements
Quantitative - Get hard data that means
something
High resolution, accuracy, repeatability
Detects leaks regardless of packaging
material:
What is leak?
It is not easy to ascertain a wide-rangingdefinition for leaks. Nevertheless, a leak maybe described as an unwanted path through
an enclosure or a wall. Although most leaks
may be found in both, vacuum andpressurized systems, some are typical for
one kind of system. For example, leaks dueto porosity are more typical to appear in the
pressurized system owed to very high-
pressure difference, while virtual leaks aremore common in vacuum systems.
To find and measure leaks there are a
wide range of methods available. These
methods include a variety of technology fromsimple to highly sophisticated ones, with a
Courtesy:Parle Technology*
*E-mail: [email protected]
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Pharma Times - Vol 41 - No. 11 - November 2009 39
- transparent or opaque
- plastic or elastic
- glossy or matte fin ish
- uni form or with print
fast and easy changeover
practical for multiple-production line
environments
low maintenance
user-friendly interface
management friendly
provides quantitative and qualitative
data collection
easy to validate; data integrity insured
network ready
Reviewing Leak DetectionMethodology
Package excitation:
A package needs to be put under stressin order to inflict a possible detectable leak.
Practically all known methods of blister
package leak detection use vacuum (orvacuumpressure) cycles. The issues
associated with it are:
a. The stress should be low enough
to consider the test method non-destructive.
b. The excitation, on the other hand,should create enough differenceof the pressure outside and inside
the blister to drive measurable airflow throughout the leak hole.
c. The transition from atmosphericpressure to vacuum takes time(evacuation time).
During this period some of the leakindicators are inaccurate. The little amount
of air present in a blister cavity may be
evacuated throughout relatively large leakbefore any measurement takes place.
Test Chambers:
Rigid test chambers are used in most
test methods.
Leak Indicators:
Leak detection methods are mostlydifferentiated by indicators employed:
1. Methylene blue dye test
2. Vacuum decay measured by:
Gauge pressure transducer
Differential pressure transducer.
3. Trace gas
4. Contact methods:
Displacement sensors
Proximity sensors
Contact load cell
5. Non-contact: Laser-based sensors
All blister package test methods thattest for leaks do rely, to some degree, onmeasuring the physical expansion,
contraction, or movement of the flexiblelidding material during the test. If a test canaccurately detect a defect based only on the
physical aspect of the leak test, it will mostlikely detect all of the critical defects. The
pressing question is, is the test truly practicalfor the needs of a blister packagingproduction line, and more importantly, is the
test truly non-destructive?
The brief description of each methodsused for leak detection are given below
1. Methylene Blue dye testing
The test sample to be leak tested is
placed in a methylene blue dye bath. Thebath is then pressurized such that if a leak is
present in the test sample methylene bluewill be forced to penetrate through the leak.The sample is then opened and inspected
visually for any traces of methylene blue dye
present inside the sample. The Blue Dye testis a huge waste of companys money. You
have to throw away every tested packwhether or not it fails. The Blue Dye Test is
only carried out every 15 minutes because it
produces so many waste blisters. Therefore,if a leak is discovered it is entirely possible
that every blister that was packed during the
15 minute period since the last test could alsobe faulty. The entire 15-minute production lot
has then to be re-worked. Along with this
other disadvantages of the traditional methodof leak testing are as follows:
in vacuum correlate to presence of leaks andmeasures quality / integrity of entire package.
The two methods used for the vacuum decaypressure method of testing of blister leak are:
Gauge PressureTransducer:
Pressure decay is an older technology
that has existed for many years. It is anindirect leak flow measurement with a leak
rate based on decay rate and test pressure.
Test volume is calculated for every set up. It
is sometimes called calibration. Differential
pressure decay offers a higher resolution and
cost when compared to pressure decay.
Pressure decay often gives an indirect
measurement when calculating leaks. The
changing test volume may give a bias
reading. The operator must frequently
calibrate during a part changeover or the
operator can zero or mask a leak.
Reference volume is required for this
method, which is about twice the volume as
pressure decay, which means twice the timeto fill for each test. A differential pressure
transducer is also required. Often, a large
(gross) leak will cause an over-range of the
differential transducer and damage or
destroy it.
Disadvantages:
The sensor measures the test pressure
or vacuum and is not adapted for
measuring in a dependable and
repeatable way tiny pressure drops.
Those instruments are used to measure
larger pressure drops. They can be
equipped with solenoid valves
(economy) or with custom designed
pneumatic valves (industrial).
Differential pressure transducer:
The instrument compares a master non
leaking part to a part under test. They are
both filled at the same time. Here two sensors
are used, one for the test pressure/
atmospheric pressure measurements, and
one with a smaller range for the minute
pressure drops.
Disadvantages:
Want to have a heating solenoid, a
moving valve seal, or just a small valve
leak needs a sometimes bulky referencepart.
You need two sensors. The differential
sensor that measures the minute
pressure drops has to have a range of
less than an inch of water but it has to
resist to the test pressure. When
measuring those minute leaks, you do
not want to have a heating solenoid, a
moving valve seal, or just a small valve
leak: the valving is an expensive
pneumatic
Observing the blue dye is cumbersome
It works for validation purposes
Extremely subjective
Destructive
Blue Dye Everywhere
2. Vacuum decay pressure:
Vacuum decay method is not a location-
specific leak indicator. It can be used with aSingle or dual transducer system. In this thetest chamber connects to vacuum test
system. Both absolute and differentialvacuum are measured in the vacuum decaypressure method. Accordingly the changes
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Pharma Times - Vol 41 - No. 11 - November 200940
3. Trace Gas:
A variety of tracer gases are available,
the most ones common being carbon dioxide(CO
2), hydrogen (H
2) and helium (He). The
measurement techniques differ greatly
according to which gas is utilized. CO2
is
detected by infra red absorption, H2
by ionselective semiconductors and He by mass
spectroscopy. The detection systems for He
are somewhat more cumbersome and costlythan those for H
2. Hydrogen also has the
advantage of simplicity of use and
accessibility with minimal training.
Disadvantages:
Sensitive
Slow test
Complex test
Potential for false readings
Lab test
4. Contact Methods:
The various contact methods used for
leak detection in blisters is described below:
Displacement sensor:
Contact sensor methods could be
destructive due to the amount of pressure
put on the flexible lidding material of a blisterpackage.
Proximity sensor:
Proximity sensors require difficult
calibration and are not maintenance free.
Changeover from one blister configurationto another is quite challenging. Variations of
the product positioning inside the blister may
produce false measurements. Proximity
sensors also are only applicable to metalliclids.
Load Cell:
Load cells can also be susceptible tothe accuracy of a tablet placement and ifthere is enough air space between lid andtop of the tablet. The initial force andgeometry of the point of contact on the lidmust be carefully evaluated based on thesize of the blister pack and materials used.Particular model of load cell (in respect tothe size and load range) could be used onlyon specific blister packs, which makes thetest method very package specific. Force
measured by load cell directly (but notlinearly) reflects pressure inside the blisterand, therefore, leak size. Nevertheless,difficult calibration is required in order tocorrelate force and leak size.
The laser scans the surface of eachpocket, measuring the height between it andthe foil. A predetermined vacuum is appliedto the test chamber. This causes the blisterpocket to develop a deflection of the foil. Asettling time takes place. This allows thesystem to stabilise. The evacuation scan isthen made.
Fig.1:Non-destructive leak testing machine
for blister packs utilizing the state-of-art non
contact scanning technology at an affordable
price. The perfect alternative for Blue Dye
test
Fig.2:The drawer of the machine is opened
and the blister pack is placed onto the plate
depending on the dimensions of the packs.
The drawer is closed to seal the test
chamber. The operator presses the START
button and the laser scanning technique
starts.
Fig. 3: Laserscan instantly pinpoints the
location of a faulty pocket seal. Further
graphical analysis is provided for eachindividual blister pocket. As shown the
machine screen shows a pass(green) or
fail(red) result for each blister pocket and also
indicates the absence of a blister
pack(black).
5. Non-contact Method:Laser Based Sensor:
Good pocket pass:
A measurement in the deflection of thelidding foil of each blister pocket is taken both
before and after a vacuum is applied to the
test chamber. This deflection is caused bythe difference between the pressure inside
the pocket and the vacuum outside. In the
case of a good pocket the lidding foil will
exhibit deflection that will be maintainedthroughout the period of constant
vacuum.The working of laser scan method incase of good pocket pass is as shown below:
Leaking Pocket:GrossHole> 30 Micron
In the case of a substantial leak path (pin
hole size) the lidding foil will exhibit little orno deflection.The working of laser scan for
this pin hole size is as shown below
Leaking Pocket SmallHole: 10 Micron-30 Micron:
In the case of micron order leak path
the lidding foil will initially deflect but then
relax after a given test period. In this case,
the change in deflection is related to the holesize or the leak path through a weak seal
area. Employing a secondary test phase can
enhance this effect which is done by the laser
sensor technique of blister leak testing
device. Also, this allows the pocket head
space to assume the same vacuum level as
that of the test chamber. After this period the
vacuum level in the test chamber is reduced.
This causes the lidding foil to become
concave, as the pocket headspace will be of
a higher vacuum than that of the test
chamber. The deflection and changes in
deflection of the lidding foil are measured by
a noncontact sensing system that scans the
lidding surface of each blister pocket. The
laser scan technique for a very minute pin
hole size is as shown bewlow.
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Pharma Times - Vol 41 - No. 11 - November 2009 41
Therefore the daily product cost of
destructive testing (not including thelabor cost, waste disposal and other
miscellaneous cost) will be the
cumulative multiplication of the above
mentioned costs i.e. $ 640
Now the one time cost of buying a laser
scan machine would be approximately$92,500
Hence the payback by using the
Laserscan machine in operating days wouldbe ($92,500/$640) i.e. approximately 145
days
Along with this the continued annualsavings by using a Laserscan machine
over a methylene blue dye test would be
the remaining 220 days of the yearmultiplied by the daily product cost of
$640 ($640* 220) i.e. $ 140800
As can be seen from the aboveexample,the traditional method of blue dyetest is a huge waste of your companys
money.You have to throw away every tested
pack whether or not it fails.However, a
Thus, The laser based sensormechanism can detect a leak in any formatof blister pocket regardless of the shape ofthe pocket or whether the contents are tabletsor capsules. It does not matter whether thelid is cold formed or thermo formed. Theoperator has no influence on the test results.Also during the test there is no contact withany contaminating substance. Whendetecting smaller leak sizes these methods
do exhibit pressures that can be considereddestructive. Non-contact laser methods aresensitive to print and reflectivity of the surfacematerial of the blister pack.
Key Benefits Of The LaserSensor Method Are:
Unlike the Blue Dye test, the laser scantest can be validated, so the results itproduces are totally objective. This alsomeans you don't need staff with specialskills to carry out the test.
The non-contact laser scanning methodis clean and dry, unlike other destructive
leak testing methods (eg MethyleneBlue Dye Test), and does not destroytest product or packaging.
Recovers costs of packaging andproduct by allowing the return of productto the packaging line.
Saves downtime by locating the precisepocket which is leaking.
An objective test with minimizedoperator error through pre-programmedtest parameters.
Reliable, validated process capable ofdetecting leaks as small as 5 microns
Automatically stores audit trail data andtest results.
The use of a non-contact sensing deviceeliminates the possibility of foil damage.
Self check of tooling before every test
Affordable tooling
Other Features:
De-skilled easy to operate.
Touch screen controls and graphicdisplay of test results.
Minimal time for product changeover.
Fast test cycle.
Example case study: To calculate howmuch money a company is losing with theblue dye test:
A company X uses Methylene blue dyetest for blister leak testing methods.
The total number of hours of productionper day for the company is 8
The total number of destructive testsperformed per hour is - 4
The number of blister packs destroyedin each test is - 4
Number of tablets in each blister packis -10
Value of each tablet is (end user price)- $ 0.5
Contact Non
Which test methods offer the Blue Pressure Trace methods: contact
following features? Dye Decay Gas Load method:
Cell Laser
sensor
Non-destructive to blisters and
product
No contact with product or
blister pack
Objectivity
Detects leaks to 10 microns
Convenient in use
Identifies individual leaking
pockets
Self validation of sensor
Tests whole web width
No limit to number of pockets
Self check of tooling before
every test
Print-out of results
Clean and dry
Can be used in production area
Affordable tooling
Bench mounting
Can be easily validated
Work station option
For further enquiries and queries please feel free to contact parle global technologies
Laserscan method is not only a clean and
dry test but is able to protect the blisterpacks
from any damage during testing.You couldsave all the blisterpacks which dont have any
leaks and put them back into theblisterpackaging line rather than throwingthem away.
Conclusion:
With the increasing, stringent demandsplaced upon by the customers in the highlycompetitive and regulated pharmaceuticalmarkets lot of care needs to be taken in thepackaging of the product. One of theproviders of the latest technology for leakdetection of blister packing being SEPHAwhose name is associated with qualitymachinery in the field of R&D blisterpackaging, product recovery and morerecently for technological breakthroughs innon-destructive leak testing.
To summarise, laser sensor detectionof leak in blisters has much more advantagesthan the traditional and other techniques
used which are listed as shown below: