Practical packaging permeability pointers

Product packaging plays a vital role in ensuring drugs reach the consumer in perfect condition by protecting against a myriad of potential hazards -from water contamination to tampering. Christopher Roberts discusses the issue of water vapour permeability

Perhaps surprisingly, one of the most damaging contaminants of drug products is water, since in the vast majority of pharmaceutical products the water content has to be accurately maintained.

Both the loss and gain of water can have potentially significant effects - water loss may lead to a change in the physical properties of a solid preparation, or a change in viscosity and concentration of vital components in liquid products, while water gain can cause swelling of water-sensitive ingredients.

Water can be a major factor affecting a product's shelf life, and those that are most vulnerable to water contamination are powders, especially inhaleables. In these products the particle size is critical for the correct delivery of the preparation, and that is significantly influenced by the moisture content.

Techniques developed for testing water vapour can be extremely useful - whether or not the product is sensitive to water - since the vapour acts as a tracer that indicates the route other gases would follow. This is especially useful where click-fit caps, threaded closures, pouches, strip packs, secondary containers, prefillable syringes, and solid seals are used, as it allows the testing of the quality of the seal under different assembly conditions, such as the torque applied.

This method can also be used to test, across a range of temperatures, the joints between materials that have different thermal expansion coefficients.

Existing legislation regarding the permeability of pharmaceutical packaging involves a number of tests - most of which are gravimetric based.

These tests often require several days to produce an accurate reading - even under ideal conditions. Anecdotal evidence suggests that they are more sensitive to the operator than is desirable. Instrumental techniques, such as WVTR meters, can be far more versatile - they are fast, reliable and can be used to test a wide range of packaging types. In many cases accurate data can be gained in as little as 30 minutes, but where low permeation is expected, the techniques can be extended to take longer time-spanned readings. They also allow the temperature and humidity of the sample to be accurately controlled.

The continuous parts of packaging, such as the walls of a bottle, the film in a sachet or the blisters in a unitary dose blister pack, are the parts that are most vulnerable to the diffusion of water.

To test the permeability of flat films, specific temperature and humidity conditions are applied to one side of the sample and a dry gas (normally nitrogen) is passed over the other side. The amount of water vapour that has passed through the sample can then be quantified, and reliable and accurate results can be obtained, sometimes in as little as half an hour.

There are two ways to test the permeability of closed containers such as pill bottles, prefillable syringes or sachets. The most reliable technique is to incorporate a water source in the container and seal it as normal. Where appropriate, this can be done on production scale equipment.

This is a particularly useful route when investigating the forming and sealing of blisterpacks, as preparing these in the laboratory may yield significantly different results from production runs. The container is placed inside a special chamber, through which dry gas is channelled. In this way any water vapour that passes through the container walls can be detected easily, and a reading can be obtained as soon as the diffusion rate is steady. Accuracy is typically in the parts per million range, or even, in some cases, parts per 100m.

permeation rates

The alternative method involves passing the dry gas through the sample container itself, and placing it in a humidity- and temperature-controlled chamber. While this provides a measure of the water vapour entering the container, it requires careful sealing where the gas flow enters the container. In most cases, the permeation rates in one direction match those in the other, and the more reliable former method is used.

Any part of the packaging can be tested for permeability - either by using a specially manufactured jig to hold just that component or by sealing off the other parts of the container using a non-permeable material.

Among the most common materials used are laminated polymeric films. While most polymers offer very good resistance to liquid water, with the exception of a few such as EVOH, PVOH and cellulose, there is little correlation between resistance to liquid water and water vapour - so a material that is good in one case might have little effect in the other. Some of the best polymeric barriers to water vapour include PVDC (polyvinylidenechloride) and PCTFE (polychlorotrifluoroethylene). The best films are laminates that include a component of aluminium, either as a discrete layer or as a result of a metallisation process.

isolating technique

In addition to these diffusion processes, it is also possible to test leakage where water passes through a gas path rather than a liquid or a solid path. This may be achieved by a variety of techniques, which usually depend on the design of the item under test. Most commonly, either a subtractive technique that eliminates the parts of the device sequentially, or an isolating technique, where only the area under test is measured, is used. Furthermore, some modern instrumental techniques permit differentiation between leakage and diffusion processes.

Many pharmaceutical companies are now using these techniques when they design their packaging, as it provides invaluable information on the protection of their products. For instance, measuring the permeability of formed materials is far more reliable than simply calculating the permeability from theoretical 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.

The rapid turnaround and versatility of instrumental techniques for testing water permeability are leading to an increase in their use by manufacturers, packaging specialists and materials suppliers. As measurements have become fast, repeatable and accurate they can speed up research. They present a real possibility for reducing bottlenecks that could be caused by adopting final hurdle, legislation-driven testing, at every stage of the process.