Originally Published PMPN September 2002
Spotlight
Picking the Right Blister Material
New materials give pharmaceutical companies even more options to choose from.
Erik Swain, Senior Editor
It used to be easy for packaging personnel at pharmaceutical companies to evaluate
and select blister materials. There was a simple assumption that could be made:
The more moisture barrier you needed, the more you could expect to spend, and
you had essentially four choices.
If little to no barrier was needed, polyvinyl chloride (PVC) was used. If a moderate barrier was needed, a coating of polyvinylidene chloride (PVdC) would be applied. Higher-barrier applications were addressed with polychlorotrifluoroethylene (PCTFE), sold by Honeywell (Morristown, NJ) under the brand name Aclar. And if 100% barrier protection was essential, the only choice was cold-form foil. Each of these fit neatly into a slot on the price versus barrier scale.
But in recent years, the picture has become much more complicated, and packaging engineers can no longer rely on the old assumptions, especially in regards to the price versus barrier scale. Honeywell has introduced new grades of Aclar that compete in the moderate-barrier market with PVdC and in the highest-barrier market with cold-form foil. The Tekni-Films division of Tekni-Plex Inc. (Somerville, NJ) has introduced a new version of PCTFE in laminate form only, sold under the brand name Vaposhield, that could further alter the cost picture for the material. Perlen Converting AG (Kennett Square, PA) has introduced a new grade of PVdC targeted to the generic drug and nutritional supplement markets that may create a cost versus barrier niche between PVC and regular PVdC. New formulations of cold-form foil have emerged that attempt to address that material's limitations. And, most radically, Ticona (Summit, NJ) has introduced the cyclic olefin copolymer (COC) material, which is attempting to carve out a niche somewhere in the middle and may end up competing with certain grades of PVdC or PCTFE.
Few of these new developments have translated into commercial products yet,
as pharmaceutical companies are reluctant to change packaging materials for
existing products, and many are not interested in pioneering new materials.
"There has not been a tremendous amount of movement," says Ed Hancock,
president of American Health Packaging (Columbus, OH), a division of AmerisourceBergen.
"The pharmaceutical industry continues to be conservative in that regard.
Nobody really wants to be the first one to use a primary packaging material,
or to entice an FDA reviewer to hold something up because of packaging."
But most are being tested on products in development, and those charged with designing packages for new drugs will need to take them into account.
PVC
PVC has long been the standard. For products that have no barrier issues, it is expected to remain the only option. Its acceptance by FDA and its ease in thermoforming means it will remain in use whenever possible.
"PVC continues to be the low-cost material of choice," says Kent Sides, business manager–pharmaceutical films for Klöckner Pentaplast of America Inc. (Gordonsville, VA). "It runs optimally on the machines. There doesn't seem to be a market for PVC replacements at all, especially in the Americas. People want to use the same products they've always used. PVC is a good, stable product."
PVdC
There weren't many options between low-barrier and moderate-barrier offerings until this year, when Perlen introduced Generex, a new PVdC offering with better barrier than plain PVC but lower cost than the traditional PVdC Duplex structure. The company envisions it as a single material that could replace both.
"This can replace Duplex for cost-efficient applications in the generics market, but it is also a replacement for plain PVC because it has a better barrier," says Dieter Feldberg, area sales manager for Perlen. "The formed version has a much higher barrier than PVC, so it costs a little more, but it makes sense with all the extra barrier you get and the yield advantage."
Generex has a yield 10% to 15% better than that of PVC, he explains.
Another Perlen PVdC product, Starflex, is positioned as a cost-effective alternative to some forms of PCTFE. "We eliminated the polyethylene (PE) in the middle and replaced it with a thermoelast, which allows for a higher PVdC concentration, well above 90 grams," Feldberg says.
Other technological advancements have enabled firms to pay less for PVdC, says John Chatillon, North American sales manager for EVC Rigid Film (Madison, CT). "In the past, to ensure an even flow, you had to have a PE layer and use the Triplex structure. Now there are more sophisticated coating lines that need less heat, and you can make 60- or 90-g structures without the PE."
PCTFE
PCTFE has seen a number of developments in recent years that have expanded its versatility. First, in the late 1990s, Honeywell introduced homopolymer versions of Aclar, which up until then had been available only as a copolymer. This, says John Blum, manager of global technical support for Honeywell Healthcare, "allowed us to produce an approximate 40% increase in barrier per mil of thickness, cutting costs from the traditional copolymer products."
Then, in a pitch for the moderate-barrier market, Honeywell introduced a coextruded version of Aclar, Cx 130E. "That product, by coextruding and providing part of its thickness as a polyolefin layer, allows us to reduce it to a barrier level equivalent to 60-g PVdC, at a lower cost," says Blum.
Now, another new Aclar product, Rx 20E, is aimed at higher-end PVdC applications. "It is targeted to replace higher coating weights of PVdC at a more affordable price than our old SupRx 900 product," Blum says.
PCTFE might also find a niche as a PVdC replacement in warmer climates, as there are concerns whether PVdC can pass stability tests for those regions at the temperature and humidity levels specified by the International Conference on Harmonization, he notes.
Another recently developed product, UltRx 3000, is trying to stretch not into the traditionally lower-barrier applications, but toward the traditionally higher-barrier ones. "It provides a barrier level high enough, in most cases, to replace cold-form foil," Blum says. "It provides significant savings in cost unless the blister is for a very, very small-sized tablet, capsule, or caplet. The cost savings are not necessarily in terms of cost per square meter of base web, but [from being able to fit more tablets into the same-sized blister] and the amount of secondary packaging that is required versus cold-form foil."
Converters are coming up with creative ways of their own to use Aclar. One example is Klöckner's SO3, a PVC/Aclar/PVC structure that "allows you to adhere to both sides of the material, or print on one side and seal on the other side," Blum says.
"It makes for a flatter package, like PVC monofilm," says Sides. "It has a lower coefficient of friction that allows it to flow through the mold better and distribute more evenly in the cavity, which makes for even better barrier."
While Honeywell's efforts have helped position PCTFE for lower-priced
uses, Tekni-Films' Vaposhield is expected to do more of the same once it
catches on. Thomas Hauser, sales manager for Pharma Flexibles, Alcan Packaging
(Kreuzlingen, Switzerland), and a former Tekni-Plex employee, says Vaposhield
"differs chemically not at all" from Aclar. Both are 100% PCTFE mass
films.
"The introduction of Vaposhield PCTFE was largely driven by global pharmaceutical clients' need for a second source of an important primary film," says Michael Franklin, vice president of Tekni-Films. "Disruption in availability of or long lead time for single-source primary packaging can have negative effects on the supply chain."
While the new material may appeal in price, Chatillon says, he questions whether it might raise specification issues. "In the short term, people may be reluctant to specify something that only one supplier has," he says. "Long-term, I think it is going to be accepted. The generic [pharmaceutical] houses are more aggressive about prices, and PACPAC [an FDA guidance expected to make switching packaging materials easier] is coming down the line."
Franklin says, however, that there should not even be specification concerns in the short term, noting that Vaposhield is a direct equivalent of Aclar. It has been approved by FDA's Center for Drug Evaluation and Research, and it is fully interchangeable on an annual reportable basis.
COLD-FORM FOIL
No one has disputed that foil is the ultimate barrier, as moisture cannot permeate it at all. But cold-form foil has traditionally been used only at the highest- end applications, mainly because of cost and design, as the standard cold forming process tends to produce wide, shallow cavities and sometimes results in cracks and pinholes.
However, this year Hueck Foils LLC (Wall, NJ) introduced a new cold-form material, called OptiForm New Generation, that aims to expand the market for cold form by addressing those issues. "This material has much better deep-draw characteristics," says Angela Roggenhofer, healthcare market manager of the Americas for Hueck. "It can cope with difficult angles and tricky tools to create deep cavities. If you are packing a big tablet in cold-form foil but want to reduce the blister size, this could be the solution. It's something to consider for applications where regular cold form does not cope well." While the new material will cost more than the old one on a per-square-meter basis, cost savings might occur because the blisters will be smaller and production efficiencies could be achieved, she says.
Another advantage of the new material, Roggenhofer says, is that it's
"absolutely chemically stable. Any product-material reactions can be avoided
even with products that contain alcohol, which traditionally could react and
cause delamination over time." That, plus the fact that some of the new
structures have better sterilizability than their predecessors, could lead to
new applications in the medical field, she notes.
Switching from traditional cold-form foil to OptiForm New Generation may not present as many regulatory hurdles as one might think, she says, because in most cases the product contact material would remain PVC, as before.
Another development in foil blisters, the entirely foil (or "all-alu") blister from Teich Constantia (Weinburg, Germany), has not caught on in North America, and industry observers don't think it will.
Hauser says Alcan's research has shown there might be technical issues
with it. "Without having PVC as a stabilizing agent and nylon as a stretching
agent, the walls have to be flatter, and the increased strain on the aluminum
could lead it to crack earlier. We've put three years of research into
it, and it didn't live up to its promises. We stopped commercialization
because the market didn't catch on."
Instead, Alcan has focused on improving its own existing structures of cold-form foil, sold under the name Formpack. The goal has been "better formability and delamination resistance, as well as expanding the field of applications to very sensitive new products, such as fast-dissolving tablets or inhaled powders," Hauser says.
However, according to Teich Constantia's Burt Zirin, "the problem
with the shape of the blister has been resolved by using a computer model. With
the right forming die, the issue of stress cracks is gone. It is true that the
shape of the cavity is different, since no PVC is used, but we have in fact
found that we actually increase production speeds slightly with the All-Alu
Blister."
Zirin says acceptance of the product has gone somewhat faster in Europe, but a number of major U.S. companies are in the final stages of development.
COC
Perhaps more than anything else, the introduction of cyclic olefin copolymer
(COC), sold by Ticona under the brand name Topas, has prompted packagers to
reevaluate what they want to put in their blisters.
COC is available in laminated and coextruded structures and tends to be positioned in the middle-barrier niche; higher than most grades of PVdC but lower than most grades of PCTFE.
"The coextrusion is in a price range a little bit higher than PVdC, and
in my view it is cost-effective," says Hauser. "The laminated version
is more expensive because you have to do more work on the material, but it has
better machinability than the coextruded version. Both materials prove to be
a bit more stable and durable than PVdC and offer a longer shelf life for the
finished blister," Hauser says.
Will it revolutionize the market for blister materials? Sandy Hoehn, marketing manager for Pharma Center Shelbyville (Shelbyville, KY), Alcan Packaging, is optimistic. "It looks like it can fill the gap between Aclar and PVdC quite nicely," she says. "We feel COC will offer a substantial cost savings compared to Aclar, making it attractive in the moderate-barrier range."
"We see it in between medium and high barrier," says Sides. "The exception would be a COC structure with PVC on one side and PVdC on the other, that could be an ultra-high end to the medium-barrier range. COC may not necessarily replace any existing technology, but it may find places in the market based on specific customer needs."
"The data we have seen so far show that COC can be a competitor in the 40 to 90-g PVdC arena and certainly can compete with Aclar on the low end," Blum says.
However, Chatillon calls COC "a long shot. Where does it fit? That question
has not been answered," he says. "If you try to compare it to Aclar,
the MVTR (moisture vapor transition rate) is not there. You can compare it to
PVdC, but COC is a carrier substrate, which makes it more
expensive."
One potential advantage of COC is that it might appeal to environmentally conscious customers. Most COC structures are entirely free of halogens, and most do not use any PVC at all, usually having polypropylene (PP) instead.
"Our job is to make sure people are aware of alternatives to the other high-barrier materials," says Rich Misdom, business development manager–North America for VAW Flexible Packaging (Mount Arlington, NJ). "Our COC coextrusion is cost comparable with PVdC-coated PVC. It's a cost-effective alternative to using PVC, especially if they also use our lidding." The offering comes in three versions to address most barrier needs in the medium to medium-high range.
Misdom adds that VAW tested its COC coextrusions on blister machines set for PVC/PVdC material, and they performed well. "The sealing temperature was raised slightly to 180–185ºC with excellent results," he says.
The last major effort to replace PVC with straight PP was undermined by machinability
issues, but that does not seem to be the case so far for COC. "There is
no curling or shrinking," Hauser says. "The laminated version can
run at speeds 30% higher than for Aclar and 20-30% higher than for PVdC. The
coextruded version is a bit slower, and the wall thickness may not be quite
as equal."
Even using COC with PP skins does not present a problem, because "PP is only a critical issue in thermoforming if it is more than 150 µm, and here it is much less," Hauser says.
Using COC with PVC skins, however, would ensure that the package would not have to change its lidding, as it would seal to foil the same as plain PVC, Sides notes.
It does appear that machinability is a concern for a single-layer variation
of COC, cyclic olefin polymer (COP), so industry observers generally do not
expect COP to succeed. "It doesn't fit well in the mold, and the barrier
properties are not kept well after forming," says Hauser.
The most significant obstacle to COC acceptance will be convincing the pharmaceutical industry that it will be worth it to change to a new material despite the stability tests that will have to be run and the regulatory scrutiny that will be invited.
"The drug industry tends to like to have lots and lots of data before they make a change," says Nic Hunt, global business director–pharmaceutical for Rexam Pharma Flexibles (Bristol, UK). "Right now the industry is not sure whether it wants to change or stay with the products it knows well. Where it will be tried is on new drugs, where they have to do stability testing anyway, or when transferring drugs to different parts of the world, where they have to run stability tests again."
CONCLUSION
There is an incredible amount of activity in blister-material development right now, which is helping to spur more activity in blister design. For example, Sonic Packaging Industries Inc. (Westwood, NJ) is using the latest in lid materials, incorporating an extra film layer that yields two extra panels for graphics, bar codes, and labeling information on a peelable lid. This is done without jeopardizing the integrity of the package and its contents. While the material adds cost, efficiency in the packaging process has not been adversely affected.
MeadWestvaco (New York City and Stamford, CT) has designed an extrusion-coated paperboard for heat sealing to blisters at lower temperatures than other products, and one of the resulting products, EasySeal Plus, is not only designed to seal to the different grades of Aclar, but to give them a tamper-evident fiber tear bond.
The question is, at what point will the experimentation end and the commercial potential be realized?
"Other products have come and gone, but the old stalwarts remain,"
Hancock says. "The barrier and protective markets are growing, but they
tend to be in the tried-and-true varieties."
Copyright ©2002 Pharmaceutical & Medical Packaging News
