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