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PRESS ARTICLE
By Christopher Roberts, Director, Versaperm
The use of plastics and related materials in pharmaceutical and medical packaging is widespread (US$18.2 billion by 2005) and growing – especially for blister packs and flexibles. This is because everyone knows that plastic packaging is impervious - it acts as a vital barrier to prevent contamination and the ingress or exit of water vapour, which is both omnipresent and insidious. Or that’s what people would like to believe! Unfortunately it’s not true.
Water, as a vapour, can pass through some plastic packaging considerably more easily than expected. It is one of the most damaging contaminants, since in the vast majority of pharmaceutical products the water content has to be accurately maintained. Water can also be a major factor in product’s shelf life.
To complicate matters still further, even an excellent barrier material can lose up to 50% of its effectiveness through thermoforming, and another 50% through heat sealing.
Water and other contaminants can and do pass through packaging. Chemical and biological reactions do occur, physical changes do take place and quality and shelf life are degraded. This article runs through many of the problems, benefits, materials and package types that are used.
Because there is no reliable way of predicting properties of a finished pack from its constituent materials (however good) and manufacturing process, medical and pharmaceutical packages must be tested if the efficacy of the drug, or the sterility of the product is not to be compromised.
Packaging
testing
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 or weeks 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. They also allow
the temperature and humidity during the testing to be accurately controlled.
Many drugs are sensitive to moisture and need high value vapour barrier films. Most polymers offer very good resistance to liquid water, with the exception of a few such as EVOH, PVOH and cellulose – but there is little correlation between resistance to liquid water and water vapour. A material that is good in one case might have little effect on the other. Some of the best polymeric barriers to water vapour include PVDC (polyvinylidenechloride) , PCTFE (polychlorotrifluoroethylene,commonly known by the trade name, Aclar), and COC (cyclic olefin copolymers)To achieve all the properties required for the application, materials are typically multilayered laminates. The best laminates for barrier properties include a component of aluminium, either as a discrete layer or as a result of a metalisation process.
PVC or Polyvinyl Chloride is the most widely used blister material – though it only provides a nominal or zero barrier to moisture and can only be used when the content do not require this protection.
PP or Polypropylene is an economical medium-moisture barrier material, though it is more common in Europe than the USA.
PVC/PCTFE Laminations is a thermoplastic film laminated to the PVC by adhesive or heat sealing, sometimes with an intermediate polyethylene layer to assist lamination. Different thickness of the composite offer average-to-extreme moisture barriers.
PVC/PVdC is a film where the PVC is coated with polyvinylidene chloride (PVdC). The coating provides a medium to high vapour barrier depending on the amount used. As with PVC/PCTFE it is supplied either with or without a middle polyethylene layer and this can effect the thermoforming characteristics of the blister.
COC or Cyclic Olefin Copolymers are a relatively new family of polymers that offer excellent barrier for applications where halogen free packaging is required. To maintain halogen free status, COC’s are normally laminated between layers of PE or PP
Cold
Form Foil is used for medicines, drugs and other products that
are extremely sensitive to either water or light. It provides an extreme
moisture barrier and is constructed using three layers: PVC, aluminium
foil, and nylon.
Table
1 Comparison of Typical WVTR’s
(Relative to PVC at 100%)
| PVC |
100 |
| PP |
15 |
| PVDC |
1.25 – 1.5 |
| CTFE |
1.0-1.1 |
| COC | 1.5-1.75 |
| Cold Form | Foil 0 |
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 blister packs, flexibles, 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 material or seal under different assembly conditions. This method can also be used to test, under a range of temperatures, the joints between materials that have different thermal expansion coefficients.
Water vapour permeability testing -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, constitute the largest surface area and are the parts that have the greatest effect on the total permeability of properly sealed packaging.
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 syringe, sachets or other flexibles. 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 an especially useful route when investigating the forming and sealing of blister packs, as preparing these in the laboratory may yield significantly different results from production runs. The container is then placed inside a special chamber, through which dry gas is channeled. 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 100 million. By running the test with a number of samples at once, the average permeability can be more accurately measured.
The alternative method involves passing the dry gas through the sample container itself, and placing it in an 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 in the testing environment, or by sealing off the other parts of the container using a non-permeable material.
The medical and pharmaceutical markets have a growing need for versatility, high performance, variety, convenience, low cost, easy packaging and new designs. This can only be filled by the innovative use of new materials and material combinations. And, of course, testing!
