Media
Article 11-12-07
Blister Pack Leak Detection: Protecting Product Integrity
Originally Published in The Pharmaceutical Solutions Update - Fall 2007
By Oliver Stauffer, Sales/Application Engineer and Heinz Wolf, General Manager - PTI
The blister packaging process for tablets and capsules is unique to the packaging industry in so many ways. Blister packaging will always exist due to its practicality; but, the things that make blister packaging difficult to work with also make it a desired product presentation.
The product is presented in a seven- or fourteencavity package to remind the consumer to maintain a dosing schedule. The thin foil lidding allows for ease of use, while a paper-foil lidding keeps kids out. Some packaging has opaque blister material to prevent children from spotting a candy-like tablet, or so that a colorful tablet will not be prone to lightbleaching.
For packaging engineers, these are practical tools for presenting the product. For a quality and process engineer, the common characteristics of a blister package provide a challenge.
There is no doubt that packing tablets and capsules is a very controlled process.
Rigid product of a fixed size is placed into a rigid cavity and flexible lidding material is stamped over it to complete the package. Tablet and capsule lines can generally handle product with relentless consistency, therefore making random defects very rare. Random defects in a packaging process are usually related to product that is difficult to place into a package with consistency, and the defect is somehow a result of the product. In an environment where random defects occur on a critical product, 100% testing should be considered. Blister packaging lines should never require 100% testing, as the process can be controlled in ways such that random defects do not occur.
Defects in the blister packaging industry are generally process-related. Foil lidding commonly used for blister packaging is highly susceptible to micro cracks which can quickly grow to leak sizes over 50 μm. Cuts on a cold-form blister package can be linked to the forming process. Any surface that comes in contact with the package has the potential to pick up debris from the packaging process and as a result will mark, crack, or cut the material. Controlling the process is the bottom line.
Most test requirements do reflect the need to control the process. With testing being completed every hour or half-hour, there is confidence in the resulting product. Most test requirements also ask for a specific number of blister package cavities to be tested, taking into consideration that each cavity is its own package.
Another interesting aspect to the blister package is that although each cavity is separate, it is also dependent. If the seal between two cavities is breached, it does not compromise the sterility or quality of the product, unless one of the blister cavities has a leak to the outside of the package.
With today's new drug delivery systems, certain drugs are extremely sensitive to moisture. In these cases, within minutes of being subjected to normal room temperature and humidity conditions, the drug delivery becomes ineffective. If there is a leak between two cavities, as the product of one cavity is consumed, the quality of the second cavity is compromised. Testing for leaks between cavities using dye migration or systematic leak testing is not common, but with new, more sensitive products, these methods need to be considered.
Systematic leak testing is best described as testing a complete package. If there are no leaks, a leak is created in a single blister cavity and the package is retested to see if the leaking cavity causes a leak in neighboring blister cavities. By systematically creating the leaks throughout the package it ensures that no leaks exist in each blister cavity. This method is not practical for most production environments, and using dye can be extremely tedious. Instead, several non-destructive methods can be considered for this application.
Blister packaging is especially unique when it comes time to test for package integrity. Historically, the dye test has proven to be the most widely accepted, and the only cost is a bucket, a packet of dye, and stained hands. While it seems simple, the production standards and product quality standards of 30 years ago are not the same. Subjectivity is coming into question, and quality lab technicians know that trying to decide whether the dye legitimately leaked into the package is tricky. For validation purposes, the dye test is common. For production purposes, the dye test becomes difficult to implement.
Like any method that has had longevity, it is difficult to simply disregard the dye test method. But, for the blister packaging industry the time has come to realize that the dye test may not be the best answer. Newer technologies are available to test blister packages quickly, effectively, accurately, and nondestructively.
The Ideal Blister Packaging Leak Tester
The ideal blister package leak testing systems do exist. The leak tester can, and should, meet the following criteria:
1. Non-destructive, non-invasive
2. Requires no sample preparation
3. Detects leaks of all sizes from 1000 μm down to 1 to 2 μm. The ability to detect large leaks is not obvious. The fact that the volume of air inside an individual blister is very small makes large leak detection quite challenging.
4. Detects leaks regardless of packaging material:
a. metal or non-metal
b. transparent or opaque
c. plastic or elastic
d. glossy or matte finish
e. uniform or with print
5. Detects leaks fast enough to make possible a high sampling rate for statistical process control (SPC) or/and 100% on-line quality control.
6. Helps with diagnostics and preventive maintenance by providing immediate data feedback, identifying defect location and frequency of defect occurrences at different times and locations.
7. Production friendly:
a. fast and easy changeover
b. practical for multiple-production line environments
c. low maintenance
d. user-friendly interface
e. management friendly
f. provides quantitative and qualitative data collection
g. easy to validate; data integrity insured
h. network ready
Challenging Application
Blister packs are considered a particularly challenging application for leak testing due to the following characteristics:
a. flexibility of the package
b. multiple cavities in one package
c. small air volume inside each cavity
d. relatively high production output on automated packaging lines
e. flexibility of automated packaging lines resulting in frequent changeovers
f. various materials used
g. expensive product packed in a relatively inexpensive container
h. highly regulated industry.
Reviewing Leak Detection Methodology
Package Excitation - A package needs to be put under stress in order to inflict a possible detectable leak. Practically all known methods of blister package leak detection use vacuum (or vacuum-pressure) 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 difference of the pressure outside and inside the blister to drive measurable air flow throughout the leak hole.
c. The transition from atmospheric pressure to vacuum takes time (evacuation time). During this period some of the leak indicators are inaccurate. The little amount of air present in a blister cavity may be evacuated throughout relatively large leak before any measurement takes place.
Test Chambers - Rigid test chambers are used in most test methods. U.S. patent 5,513,516 describes use of a flexible chamber wall (bladder) for leak testing flexible containers using vacuum decay method.
Leak Indicators - Leak detection methods are mostly differentiated by indicators employed:
a. Bubbles of air formed and visually detected in the water (destructive method)
b. Ink penetrated inside the blister and visually detected (destructive method)
c. Deformation of the lid detected by:
• contact displacement sensors
• proximity sensors
• non-contact
ii. laser-based sensors
iii. indirect non-contact imaging
d. Lid stress detected by contact load cell
e. Vacuum decay measured by:
• gauge pressure transducer
• differential pressure transducer.
Dynamics of a Blister Pack
The typical blister package has very little air inside the package cavity, and under any normal vacuum test, any leak greater than 50 μm would not be detectable. The assumption is that initially air inside the blister is under atmospheric pressure 101 kPa [14.7 psi] when the blister pack is placed into the 70 kPa [10 psi] vacuum (30 kPa [4.7 psi] absolute pressure) chamber. At this condition, air flow throughout a 50 μm [2 mils] hole would be about 21 std cm3/min [0.35 cm3/s]. Therefore, large leaks (above 50 μm) would be equalized during evacuation time of one second and nothing would leak after that.
Leaks that are smaller than 50 μm would be detectable measuring the pressure drop alone. The key is then to detect not only the small leaks of a blister package, but to detect leaks that are greater than 50 μm.
In the end, most defects created in the blister packaging process are greater than 50 μm and are somehow related to the process.
All blister package test methods that test for leaks do rely, to some degree, on measuring the physical expansion, contraction, or movement of the flexible lidding material during the test. If a test can accurately detect a defect based only on the physical aspect of the leak test, it will most likely detect all of the critical defects. The pressing question is, is the test truly practical for the needs of a blister packaging production line, and more importantly, is the test truly non-destructive?
Unsupported Lid
Using a test method in which a vacuum is pulled on the blister package, the lidding is not supported and is allowed to fully expand. Below is a simulated stress analysis of a cavity under such a test. This type of test could be any method that is looking purely at the expansion and contraction of the lidding of a blister cavity using non-contact methods, or the water bath and dye test. The water bath and dye test provides no support to the blister package lidding.
Non-Leaking Sample
Deformation
The maximum deformation accrues to the center of the unsupported lid and estimated 200 μm [8 mils]. Estimated change of the volume of the air inside the blister is 0.13 cm3. Estimated pressure of the air inside the blister is 75 kPa [11 psi]. Therefore, the pressure differential is only about 45 kPa [6.5 psi]. At this condition the flow rate of 1 std cm3/min corresponds to a hole size of 12 μm [0.5 mils].
Stress
Red and yellow areas indicate stress above yield strength of material. The analysis shows dangerous stress concentration in the middle of the unsupported lid as well as on the inner edge of the seal. At these conditions the test is destructive. Reducing the test vacuum down to 30 kPa [4.3 psi] could make it nondestructive, however, less sensitive.
Leaking Sample
If the pressure in the vacuum chamber and inside the blister equalizes fast enough due to a relatively large leak, no deformation or stress of the leaking blister would occur. However, plastic (nonelastic) deformations can occur during evacuation time if the chamber is being evacuated faster than the blister throughout a relatively small leak. Since there is no significant force pressing the lid down, it would stay deformed (domed) even after the air from the blister is evacuated throughout the leak and the pressure in the vacuum chamber and inside the blister equalizes. Therefore, a blister with a small leak may be deformed the same way as a non-leaking blister.
Conclusion
The blister pack leak testing methods with unsupported lids are most likely destructive. Water bath bubble as well as vacuum decay tests could likely leave relatively large leaks undetected, and the method requires an operator to carefully look for any migration of dye into the package. With the best eyesight and even test conditions, false positives and negatives will still occur. Non-contact proximity and laser-based deformation sensors work only with relatively large leaks. The deformation of the lid (or lack of deformation) cannot be positively correlated to the leak size.
Lid Supported By Contact
Sensor - Non-Leaking Sample
Some methods use a displacement or contact sensor to measure the amount of pressure produced by a fully expanded blister package. If the pressure against the sensor reduces during the cycle of the test, the package has an air leak and is defective.
Deformation
The maximum deformation accrues in the midsection of the lid and estimated 37 μm [1.5 mils]. However, the deformation at the center of the lid is only about 20 μm [0.8 mils]. It means that the contact displacement sensor needs to have very low displacement force (less than 150g) to allow measurable displacement. Estimated change of the volume of the air inside the blister is 0.02 cm3. Estimated pressure of the air inside the blister is 96 kPa [14 psi]. Therefore, the pressure differential is about 64 kPa [9.3 psi].
Stress
The analysis shows dangerous stress concentration in the contact point on the lid. At these conditions the test could be destructive.
Lid Supported By Contact
Sensor - Leaking Sample
Deformation
With estimated deformation only 100 μm [4 mils] the deformed lid rests on the tablet; therefore, the result depends on tablet placement.
Stress
Insignificant stress of the lid is estimated.
Conclusion
Non-contact test methods have their nuances, and the method is either subject to very critical and highly sensitive height measurement, or the operator's subjectivity in observing the presence or absence of dye inside the package cavity. Deformation measurement of the flexible lidding material is not as sensitive as other methods, but when detecting smaller leak sizes these methods do exhibit pressures that can be considered destructive.
Contact sensor methods could be destructive due to the amount of pressure put on the flexible lidding material of a blister package. Load cells can also be susceptible to the accuracy of a tablet placement and if there is enough air space between lid and top of the tablet. The initial force and geometry of the point of contact on the lid must be carefully evaluated based on the size of the blister pack and materials used. Particular model of load cell (in respect to the size and load range) could be used only on specific blister packs, which makes the test method very package specific. Force measured by load cell directly (but not linearly) reflects pressure inside the blister and, therefore, leak size. Nevertheless, difficult calibration is required in order to correlate force and leak size.
Lid Supported By Flexible
Bladder - Non-Leaking Sample
Deformation
Deformations on the lid and blister are insignificant (less than 3 μm [0.14 mils]).
Stress
Stress is not significant; calculated factor of safety is 2.6. The test is non-destructive.
Lid Supported By Flexible
Bladder - Leaking Sample
Deformation
The maximum deformation of the lid (and bladder) observed around the tablet. It is estimated 250 μm [10 mils].
Stress
Whole lid is stressed above the material yield strength. Test can destroy leaking blisters.
Conclusion
There are several important facts regarding some of these methods. Contact and proximity sensors require difficult calibration and are not maintenance free. Changeover from one blister configuration to another is quite challenging. Variations of the product positioning inside the blister may produce false measurements. Proximity sensors also are only applicable to metallic lids. Non-contact laser methods are sensitive to print and reflectivity of the surface material of the blister pack. Vacuum decay method is not a location-specific leak indicator.
Use of a flexible bladder makes the test truly nondestructive. Deformation difference between nonleaking and leaking samples is 20% larger than it is on unsupported lid tests. It is significant and could be reliably measured by indirect imaging or noncontact laser-based scanning.
Deformation of the bladder directly (but not linearly) reflects pressure inside the blister and, therefore, leak size (particularly, for relatively large leaks). The same bladder could be used for a large variety of blister packs regardless of size and materials used.
Use of a flexible bladder creates the most favorable conditions for the vacuum decay test including:
a. minimal possible test chamber volume
b. non-expansion of the blister during the test maximizes pressure differential.
Vacuum decay is linearly proportional to the leak flow and, therefore, tests can be calibrated easily.
About The Authors
Oliver Stauffer received his bachelor of science degree from the University of Michigan. His expertise and focus has primarily been new technologies and test method development specific to package testing. Stauffer joined PTI in 2005 as a member of the research and development team working on non-destructive testing of blister packaging. In 2006, he joined the sales team as a sales/applications engineer for PTI Inspection Systems.
Heinz Wolf received his bachelor of science degree in mechanical engineering from the Ingenieurschule Biel-Bienne in Switzerland. Wolf joined PTI in 1985 as a service engineer. He joined the sales team in 1996 and has held the position of general manager of PTI Inspection Systems since 1997.