PRESS ARTICLE

Practical Pointers for Packaging Permeability
How to test pharmaceutical packaging quickly and accurately for water vapour permeability and leakage.

Introduction

During the development of pharmaceutical products, a significant effort is made to ensure that the products reach the end user in an acceptable condition. The most significant factor apart from the formulation of the product itself, is the primary packaging into which it is placed. This must protect the product against a myriad of potential attacks, from contamination to tampering. One potentially devastating contaminant, perhaps surprising because of its normally life-giving status, is water. In most pharmaceutical products, the water content has to be accurately maintained. Water loss will cause drying out; in the case of liquid preparations, the viscosity or concentration of active components may be increased. Water gain may cause swelling of water sensitive compounds which is especially significant in orally administered preparations which are designed to be water soluble. This may have a number of knock-on effects. However, the most critical type of preparation with respect to water vapour contamination are powders, especially those prepared for inhalation.

Packaging Testing

Legislation governing pharmaceutical packaging testing provides a number of tests, mostly gravimetric based, which can take several days to achieve an accurate reading under ideal conditions. The regimes typically define the testing conditions, although the tests can be modified for specific requirements. However, for packaging designers, instrumental techniques have been developed which are capable of providing fast and reliable measurement of a broad range of packaging types. These techniques provide a level of versatility and an ability to identify weak points in the packaging design and materials previously unavailable, or impractical. The instrumental techniques also permit the accurate setting of temperature and humidity conditions.

Water Vapour Permeability Testing

Diffusion occurs through continuous parts of the packaging, such as the walls of a bottle, the film in a sachet or the blisters in a blister pack.

Flat films are commonly tested by applying the temperature and humidity conditions to one side of the sample, and passing a dry gas, usually nitrogen, over the other side. A detector will then quantify the amount of water vapour that has passed through the sample. Equilibrium may be achieved in as little as 30 minutes.

Bottles, sachets, blister packs or other closed containers can be tested in one of two ways. The better technique is to incorporate some water in the container before sealing in the normal way. This is then placed in a chamber in the instrument, through which the dry gas is passed. Any water vapour passing out of the container is passed to the detector which provides an accurate reading once a steady state of diffusion is attained. The second technique is to attach the gas flow to the test container itself, and place the test container into a temperature and humidity controlled chamber. The dry gas is then passed inside the test container and any water vapour entering the test container is measured. The latter technique has the disadvantage of requiring careful sealing where the gas flow enters the container, but is useful in some circumstances.

In its most basic form, the technique for measuring closed containers provides the permeability of the whole container, but it is possible, for example, to seal off the closure with a non-permeable material, and thereby calculate the permeability of the bottle apart from the closure. Any component in the packaging can be measured, either by subtraction, or the manufacture of an appropriate jig to hold the component with the humid environment on one side and the dry gas on the other.

Leakage Testing

Quite apart from the diffusion processes occurring in packaging, there are often leakage process, where the water vapour is able to pass through a gas path, as opposed to a liquid or solid path. In some instrumental techniques, it is possible to differentiate between diffusion processes and leakage processes.

For many applications, the water vapour testing technique is used for leak testing whether or not the product is water sensitive. In this case, the water vapour is used conveniently as a tracer as it will indicate the route that other gases may follow. This is especially useful for solid seals, as it allows the testing of the quality of the fit, perhaps under different torque setting conditions, and at different temperatures. However, the jointing of any dissimilar materials will benefit from such an analysis.

Design

While the techniques described above are used by many manufacturers supplying packaging to the pharmaceutical industry, many major pharmaceutical companies have adopted these in the packaging design phase of their product development, to supplement and confirm information provided by their suppliers. For example the measurement of permeability of formed materials is significantly more reliable than using calculations of permeability based on data for flat films. With increasing innovation in packaging and the need for novelty in OTC marketing especially, the norms and limits of packaging materials will continue to be stretched, further enhancing the need for ad hoc testing.

Conclusions

A growing number of pharmaceutical manufacturers and their suppliers have found that the rapid turnaround and versatility of the instrumental techniques are an aid to speeding up the pace of research. These present the possibility of reducing bottlenecks that might be caused by adopting final hurdle legislation-derived testing at every stage of the race.