Issue link: https://www.e-digitaleditions.com/i/733311
Tablets & Capsules October 2016 33 blister package and degrade its con- tents usually depends on the size of the leak. With blister packaging, even tiny leaks can be a problem. Given the relatively little headspace—about 0.25 cubic centimeters—in most blister cavities, oxygen and moisture can reach critical levels within hours. For example, a foil defect equivalent to a 10-micron pinhole can allow a flow rate of 0.84 cubic centimeters per minute. Depending on the pressure, temperature, and duration of exposure, it doesn't take long for contaminants to find a path through a channel leak in the seal and/or through a series of many microscopic flex cracks. Several methods are available to leak-test blister packs, and each has its advantages and drawbacks. The ideal method is simple, reliable, and line- ready. Unfortunately, the most com- mon method remains the blue dye test, which has been in use for decades. I call it unfortunate because a dye may fail to identify tiny leaks in packages of critical products, a fact recognized by the US Pharmacopeia, which revamped USP General Chapter <1207>: Container Closure Integrity Testing [1]. The chapter now encourages manufacturers to use tests that are more quantitative and reliable, which reflects the need to address the requirements of today's higher-risk products, as well as the availability of better technologies. Subjectivity and variability mar results To conduct the blue dye test, one or more blister packs is submerged in a chamber containing the blue liquid and a vacuum is drawn. The chamber is then brought back to atmospheric pres- sure, and the packages are retrieved and inspected to see whether any dye has entered them. If no dye is present in the blister package, no defect is detected. The method's major fault is its reliance, in most cases, on a timer dur- ing the vacuum phase, even though Leak-testing blister packages: The limitations of the blue dye method Oliver Stauffer Packaging Technologies and Inspection Blister packages are a convenient format for consumers and a practical approach to preserving the quality of tablets and capsules. Most blister package applications are considered low risk, and do a very good job of protecting drug products from the ingress of moisture, which may lead to product degradation. Tablets of a hydrophilic nature—a tendency to absorb moisture—are especially in need of such protection. New medicines require new tests In recent years, however, concerns about the integrity of blister packaging have increased as the number of hor- mone-based and steroidal treatments has grown. Packaging these and other classes of drug products is considered a high-risk application given their potential to deteriorate and affect treatment results. To counter that, manufacturers typically opt for a fully aluminum, cold-formed package, which provides the best protection against the ingress of oxygen, although some companies have pack- aged highly sensitive steroidal treat- ments in thermoformed blister packag- ing. Whatever the packaging used in this high-risk application, it's very important that you check for micro- scopic leaks, as these products are more sensitive to environmental con- ditions than most other tablets and capsules. The amount of environmental con- tamination (moisture) that can enter a the blue dye only enters the package after the vacuum phase. Thus, when operators return the chamber to atmospheric pressure, nothing res- trains them from immediately remov- ing the packages from the dye during this critical final stage. The blue dye test is also subject to other variables that are not easy to control, including package headspace and dye surfactant concentration. In fact, the test really only tells you how easily or rapidly the dye can enter the blister cavity. It gives you no informa- tion about the ingress of oxygen or vapor. That's a major drawback because these gaseous contaminants can pene- trate foil and film through a small leak or a series of micron-scale leaks more easily than the liquid dye, which is sub- ject to surface tension and requires a relatively large single passage to enter the package. The subjective nature of the operator's inspection is another major disadvantage and difficult to monitor. Although a comprehensive standard operating procedure, coupled with training, can mitigate subjectivity, there is no way to eliminate it. Furthermore, most dye-based leak tests are validated by using a needle to prick a hole, and most test apparatuses A number of technologies offer better relia- bility than the blue dye test, including volu- metric imaging under vacuum. Shown here are screenshots of blister packages that failed and passed tests conducted using PTI's VeriPac UBV. If a test doesn't give reliable results, it's not really a test method.