Pharmaceutical and Medical Packaging News Magazine
PMPN Article Index

Originally Published November 1998

SPOTLIGHT

A Blistering Pace

New ways to use materials and more flexible machinery are both driving the development of blisters.

by Erik Swain, Senior Editor

Blisters are probably the fastest-growing segment of the healthcare packaging market, and are expected to attain a 40% share by 2003, reports a study by Find/SVP Inc. (New York City). Several new developments are driving such growth.

Blisters are the dominant form of drug packaging in Europe, and they are becoming more accepted in the United States as pharmaceutical manufacturers and consumers realize how blisters can help patients follow drug regimens, how they protect a drug over a long shelf life, and how portable they are.

Blisters used in the United States are traditionally thought of as being thermoformed film, usually polyvinyl chloride (PVC), and foil. But with the advent of new drugs that need to be packaged in higher-barrier materials, different solutions are emerging, including new kinds of film, new foil-to-foil packages, and an increase in cold-forming methods. Materials and machinery suppliers and contract packagers are often at the forefront of these developments, advising end-users on new ways to meet their needs.

Compliance and marketing considerations are among the factors in the use of blisters, says Kumar Nanavati, director of packaging development for Whitehall-Robins Healthcare (Madison, NJ), a division of American Home Products Corp. "We package in large bottles, small bottles, and blisters, and we will use just blisters when a product requires compliance," he says. "But sometimes a single-layer HDPE (high-density polyethylene) bottle does not give you the proper light protection. An amber bottle can, or you can go to an amber-color blister, or a clear blister that can absorb ultraviolet rays and put it in a folding carton."

THE IMPORTANCE OF BARRIER

The most noteworthy developments are in materials. But not new ones. "There are more blisters being derived and created out of existing technology," says David R. Sciubba, healthcare sales manager, Hueck Foils LLC (Wall, NJ). "Fine adjustments, not revolutionary. A different heat-seal coating to seal to a different substrate, for example."

Blisters can act as a barrier to three things: moisture, light, and oxygen. Of those, moisture currently seems to be the highest priority because many new drugs, especially ones developed through biotechnology, are highly sensitive to water. This, in turn, has produced a demand for blister materials with higher moisture barriers.

"The latest generation of directed drugs are all carefully tested for stability, and, in many cases, launched globally with very specific barrier properties," says Michael Franklin, vice president of Tekni-Plex Inc. (Somerville, NJ). "We are definitely seeing an increase in the use of higher-barrier films in order to pass current ICH requirements on the first attempt. Due to the enormous cost of drug development, there is a tremendous financial penalty as a result of the delay incurred by not being able to get a new product to market because the packaging has failed stability. Therefore the cost of high-barrier packaging film is insignificant in the global sense."

COLD-FORMED FOIL

Those who need the highest degree of protection are opting for an all-foil package produced by cold forming. "We are seeing specific growth in cold-formable foils," says Sciubba. "More moisture-sensitive drugs are being put out on the market. Cold-formable foil is finding a home because it's the only material where you truly get a 100% barrier to moisture, oxygen, and light."

This has helped expand the applications for blisters, says Tim McBride, vice president of sales and marketing at Sharp Ivers-Lee (Conshohocken, PA). "Cold-form foil blister packaging is increasing the ability of the blister to be used more ubiquitously for sensitive products," he says.

The cold-forming process doesn't use heat; rather, the foil is shaped and molded around a plug to form a cavity. As such, it is a marginally more expensive process than thermoforming, and its tooling is a bit more expensive than that of thermoformers. But cost takes a back seat when packagers face stability issues and are trying to get the product to the market quickly, says John Hopkinson, general manager at Service Industries (Rolling Meadows, IL), a division of Thomas Engineering Inc. that makes tooling. "You must have a product to justify it," he says. But "our orders for cold-form sets are up 200% from last year. A lot of people are calling us about machine upgrades for cold forming."

Perlen Converting's PVdC-coated PVC film is designed for high-barrier pharmaceutical packaging.

Upgrading is an option for many companies. "Most new machines are equipped to be capable of being converted to cold-form aluminum," explains John Soporowski, pharmaceutical sales manager at Klöckner Medipak (Clearwater, FL). "Five years ago, they wouldn't elect that option. Now, 70–80% do. The cost is much lower when you do it initially."

One disadvantage is that the cavities must be made fairly large in the cold-form process, limiting the number of pockets a single blister can include.

FILMS

For those who must use film but need a very high moisture barrier, AlliedSignal Specialty Films (Morristown, NJ) recently introduced UltRx 3000, a 3-mil Aclar barrier film, which is "the highest moisture barrier available on a clear film," says John Blum, healthcare technical specialist at AlliedSignal. He says Aclar, which is easily thermoformable, has benefited from the trend toward using higher-barrier materials. He notes that another film, one with a lower barrier and some properties similar to materials with polyvinyl dichloride (PVdC), may debut by the end of the year.

This, too, has been a big boon for blisters, McBride says. "A number of newer Aclar products, which give a clear or tinted see-through of the thermoformed blister cavity, give properties closer to the near-perfect barrier offered by a foil, and have allowed a wider use of blister packaging," he says.

Aclar is often used in conjunction with PVC because the latter seals better. But that may change. "It's up to the blister people to come up with something that can seal directly to that Aclar," says Patrick Dent, marketing manager for pharmaceutical packaging at Reynolds Metals Co.'s flexible packaging division (Richmond, VA). "Usually, you have 10-mil PVC and 2-mil Aclar, and you seal to the PVC side. But when the product is extremely sensitive, the 10-mil PVC is the chink in your armor. Between the foil and the Aclar is the PVC, and moisture and oxygen can penetrate there. People are looking to seal to the Aclar side, or to do pure Aclar. The benefit is similar to cold forming, and you can see the product. But the technology to seal to that is very difficult."

Blisters' popularity is being driven not only by Aclar, but also by other films such as PVC, PVC/PVdC, and PVC/polyethylene (PE)/PVdC, says Kent Sides, pharmaceutical films business unit manager at Klöckner Pentaplast (Gordonsville, VA). Klöckner supplies all four materials, among others, and recommends one based on the customer's specific needs.

"PVC is highly machinable, clear, and heat sealable to a wide range of lidding materials," he says. "PVC/PVdC has good clarity and thermoformability, and is a good oxygen and moisture barrier. PVdC is very cost-effective, and we can customize coating weight depending on the requirements of the customer." In fact, he says, PVC/PE/PVdC with a heavy coating weight of PVdC "overlaps in properties with some of the Aclars."

Perlen Converting AG (Princeton, NJ) markets Perlalux, a PVdC-coated PVC film. It has replaced the inner layer of LDPE with a thermoelast to improve bond strength and to provide more yield at the same conditions for water vapor barrier, thermoforming, and machinability.

Then there is polypropylene. At one point it was touted as a possible replacement for PVC, especially in Europe, where the environmental activists in some countries have claimed that waste from PVC can be toxic. But, says C. Jeanne Taborsky, a consultant based in Columbia, MD, the impetus to use polypropylene has waned because of certain drawbacks. "While U.S. firms seemed to want to pursue polypropylene blisters, it presented problems (the need for plug assist or the purchase of different form-fill-seal machines) that caused them to back away. Polypropylene is used in the United States for the manufacture of closures and as inside layers on certain foils, and is the material of choice in prescription vials.

She says the advantages of polypropylene include easy recyclability, lack of toxins released during incineration, and a good moisture barrier, but its biggest drawbacks are that it's "difficult to run on a standard blister machine" and it cannot be processed as fast as PVC. If a company wants to run polypropylene and it needs to get a new machine, it must go through validation. And it must perform a variety of tests on the polypropylene to satisfy FDA requirements if it wants to add the material to its offerings, she says.

As a result, polypropylene is virtually nonexistent in U.S. healthcare blisters (except, says Taborsky, as a plastic lining on certain foils), and appears to be used minimally for that purpose in Europe, though it is unclear how many European companies are still trying to develop a polypropylene blister for pharmaceuticals.

Uhlmann's UPS 300 M mini blister packager can produce up to 200 blisters per minute.

Dan Gerner, president of Packaging Coordinators Inc. (Philadelphia) and the vice chairman of the Healthcare Compliance Packaging Council (HCPC; Washington, DC) notes that another advantage of polypropylene is that it can be used to make the entire blister, making recyclability even easier. For the same reason, some suppliers are developing an all-PVC blister, he says. Klöckner Pentaplast says they are the only supplier who has brought one to market thus far.

THE MACHINERY EFFECT

The developments in materials have had an effect on machinery, which has had to become more flexible to accommodate as many formats as possible. "Our machines can handle all the materials that people ask for—PVC, aluminum, and polypropylene," says Angelo Schepis, executive vice president, Marchesini Packaging Machinery Inc. (West Caldwell, NJ).

Soporowski cites servo technology as an important development. "It allows you much more precise control of cycling times, which can allow you to have longer dwell with shorter index times." Also, he says, new machines have much more accessible touch-screen interfaces and can show the precise forming and sealing pressures, which aids in machine performance and validation.

Matt Neumann, vice president of operations, Uhlmann Packaging Systems Inc. (Towaco, NJ), notes that "what we added was a completely laser-controlled machine index. This technology is even good for lights-out machine operations. The index pulls as much material as necessary, such as positioning the blister precisely in the sealing, the perforation, the coating, and the punch stations. There is less setup time, less waste, and in-process control. The next revolution will be to start using industrial PCs as the machine controller. They would have input and output cards and run under Windows NT. There would not be any proprietary programming language any more."

The growth in blisters has also produced innovations in other kinds of machines, from deblisterers, like those offered by Gemel Precision Tool Company, Inc. (Ivyland, PA), and Sepha Products (Irvine, CA), and leak testers for blisters, such as the new Qualipak 730 from ITI Qualitek (Billerica, MA).

Contract packagers have also seen a rise in blisters. "More pharmaceutical companies find outsourcing a cost-effective alternative to doing the packaging in-house," says Drew Hoffman, sales and marketing manager, Sanofi Pharmaceuticals Inc. (St. Louis). "In addition, nutritional supplement companies have begun to market their products in blister form to give an added value to the consumer in an already highly competitive market."

FUTURE PROSPECTS

Blisters will benefit from regulations, such as the one requiring unit-dose packaging for products with a certain level of iron. And they will benefit from new applications, such as "transdermal patches, granules that can be mixed in the cavity itself, and unit-dose liquids," says Ray Trucksess, director of sales at Comar Inc. (Buena, NJ). Finally, they will benefit from creative new ways to use materials and machinery to meet a drug's or supplement's requirements. As more people in the healthcare industry think about how to use blisters, chances are the public will as well.

Photo courtesy Tekni-Plex/Photographer Joseph E. Coscia/Photo collage by James Schlesinger