Medical Device Link.

BLISTERS

Alcan Packaging offers both lidstock and base webs for blister packaging.

As convenience and compliance concerns provoke interest in unit-dose packaging, film developers and converters have responded with continuous innovation in blister materials and packaging systems.

Lidding material designs aim for consumer-friendliness, and lidding paper must allow for the clear, legible printing of small bar codes. With the mounting demand for high-barrier materials for packaging moisture-sensitive drugs, film and foil suppliers have sought to address material costs.

And yet one relative constant has been the preference of many pharmaceutical firms for foil in blister packaging. In some cases, this derives from standing investments in blister machines configured for cold forming. Companies often want to use foil to ensure that products will pass stability testing without issue in order to get to market as quickly as possible.

Some companies convert from thermoformable film to foil when launching new moisture-sensitive drug forms, such as extended-release drug versions. “Many of the rapid-release and long-acting-release drugs are hygroscopic by nature. Companies will move to foil where the original drug actives might have been a very stable product packaged with PVC,” says Bill Sharpless, global marketing director, Alcoa Packaging (Richmond, VA).

While foil provides the necessary barrier that some products require, it often leads to a much larger package, since foil blisters require more sidewall draft. This creates added costs from factors such as higher capital investment, fewer tablets being packaged per forming stroke, additional secondary packaging, and restrictions on compliance-enhancing formats.

Angela Roggenhofer, healthcare account specialist, Honeywell Specialty Films (Morristown, NJ), says that companies should adopt a total cost approach when evaluating blister material options. Since foil may cost less on a square meter basis than some high-barrier films, “we see a lot of resistance from purchasing managers [to convert to thermoformable materials, even though thermoforming provides a more cost-effective alternative,” she says. In foil packaging, “millions of dollars” in added costs are incurred throughout the life of the drug. Foil costs add up in areas such as drug product and material waste, storage, and quality control, Roggenhofer says.

WEIGHING COSTS

Honeywell offers the Aclar Value Calculator for comparing the costs of foil and thermoformed materials. In the application, companies can use their own production parameters to forecast and evaluate material and production costs from product launch to patent expiry.

“We are making this available to our end-user customers, as packagers increasingly look for safe, cost-effective alternatives in higher-barrier materials for their moisture-sensitive products. The Aclar Value Calculator is unique because it allows pharma to evaluate total packaging costs using their own internal parameters, ensuring selection of the right barrier materials, at the right cost, regardless of tablet size, shape, or quantity,” Roggenhofer says.

Mike Bost, marketing manager of Aclar laminates, Alcan Packaging Pharma Center (Shelbyville, KY), says that total packaging costs will vary with factors such as package configuration and production requirements. Solutions are tailored to customers’ specific needs. “At Alcan Packaging, we don’t take a biased position with our material recommendations. We can provide customers with the technical information on FormPack cold-form aluminum foil or any of the various Aclar structures, and then let the customer decide on the best barrier material for the application,” Bost says.

Bost notes that barrier requirements may dictate the packaging regardless of the cost. “If [our] customers want the ultimate barrier for a reasonable cost, they generally go with our FormPack product,” given its moisture-, oxygen-, and light-barrier properties,” he says.

“UltRx 2000 is the Aclar grade that is most often compared with Alcan Packaging’s FormPack,” Bost adds. “UltRx 2000 lets in very little moisture, but significantly more oxygen and light than FormPack, unless you pay the up-charge for an amber PVC [for light barrier]. The barrier comparisons become even more divergent when you are drawing Aclar laminates down” to create blister pockets for drugs.

“Aclar laminates will be more cost-effective in some cases. Cost-saving factors such as in-line speeds and cartoning are less [certain],” says Bost. “The only sure savings stem from material reduction where the size of the blister cavity can be reduced.” When absolute barrier isn’t required, “large tablet packaging might favor the economics of the thermoformable materials. That is the single strongest factor favoring Aclar laminates in a cost comparison between the two materials,” Bost says.

Alcoa Packaging has developed a foil laminate in among its Cold Form 3000 series that allows for a deeper draw and thus closer nesting of foil cavities, supporting foil material cost reduction, says Alcoa’s Sharpless.

“When utilizing a high-pressure cold-forming process, we have drawn blisters to a 60-degree radius. Laminates in our Cold Form 3000 series then start to compete against plastic in many applications,” he says.

In testing with a 1-in.–diameter round tool, the polyamide/foil/PVC laminate was drawn to a depth 30% greater than the standard commercial draw depth without affecting machine speeds.

MULTIPLE PUT-UPS

American Health Packaging (Columbus, OH) packages solid-dose product in PVDC-coated PVC, Aclar laminates, and foil for customers with barrier requirements.

Clients employing thermoformable materials often take one of two approaches, says Michael Rathburn, vice president, manufacturing. Some run concurrent stability tests, such as by testing a PVC package and a higher-barrier laminate and then adopting the most-economical film that ensures stability and dating requirements. “This is generally done for new drugs or by generic companies that want to be first to market with a new drug coming off patent,” he says.

Other companies with moisture-susceptible product will test one high-barrier material. “We might put them up on Aclar UltRx 3000 when we know that it will pass stability. They might have a lot of [other] product in that film. It becomes more economical from an investment standpoint,” Rathburn says.

“Our customers are often looking to do at least two stability packaging putups,” says Paul Glintenkamp, director of pharmaceutical packaging, Packaging Insights and Carton Services Inc. (Norris, TN). “We are seeing the increasing use of Aclar with the prevalence of moisture-sensitive orally dissolving and chewable tablets.” One client, for example, is currently evaluating Aclar 190 versus different strengths of Aclar S03, he says.

Packaging Insights will develop and design alternative packages when assisting customers in blister price evaluation. A recent customer was “teetering between a cold-form package and a high-barrier Aclar.” Packaging Insights produced a cold-form design and one using Aclar S03. “Our goal was to meet their marketing and production needs, while showing the cost differences for each case,” says Glintenkamp.

“We know hands down that cold-form will address their barrier needs. But, using foil you will not be able to fit as many cavities on a blister. You either have to make the blister considerably larger, or use twice as many cards. Aclar can be considerably more expensive, but you can put more tablets on the card and in the end, use less material,” Glintenkamp says.

“Each project has its own specifics and must be handled on a case-by-case basis to provide the customer with the best solution,” he adds.

Some converters are testing the use of Aclar as the interior or contact layer of blister laminations. In this application, the lamination film is inverted, using Aclar-In. Hueck Foils (Wall, NJ) is one company that offers lid stock with a proprietary adhesive layer that seals directly to the Aclar.

Alcan Packaging is testing sealants for this application, says Bost. “We are testing three very promising heat-seal systems that are applied to the foil lid stock. Some customers have requested a universal solution that would stick to PVC and Aclar, since the vast majority of laminations feature PVC as the inner layer,” he says.

Converters have faced a challenging task in developing heat-seal coatings for this application. “PCTFE is very similar to Teflon—it’s nonstick,” says Roggenhofer.
Yet using Aclar as the interior layer provides multiple advantages, she says.

“It is a superior contact layer because it is chemically inert and biochemically stable,” she explains.

Also, in laminates with PVC as the contact layer, moisture enters through the seal/adhesive layer and the PVC layer at the flange. PVC has 10 times the moisture-vapor transmission rate (MVTR) per mil compared with Aclar. In the Aclar-In configuration, the high-barrier Aclar is right up against the foil lidding, inhibiting moisture ingress.

“The improvement highly depends on blister design. We have found Aclar-In to provide 15% moisture-barrier improvements compared with Aclar situated on the outside of the laminate,” says Roggenhofer. “This offers downgauging potential. You can achieve the same barrier with a thinner-gauge Aclar, or increase your moisture barrier using the same thickness.”

THERMOFORMING CHOICES

Rathburn says that the Aclar-In configuration would potentially provide alternatives to companies looking for higher barrier choices in thermoformed blisters.
“If a drug came out that required a higher barrier to pass stability, and the film was easier to work with and offered cost advantages, it might be a suitable alternative. Or you could place more dating on the product [such as moving from] two year’s to three year’s shelf life,” he says.

Film makers such as Alcan Packaging, Klöckner Pentaplast (Gordonsville, VA), and Tekni-Plex (Somerville, NJ) offer clear high-barrier films incorporating Topas COC (cyclic olefin copolymer).

“We have seen a steady adoption of Topas COC in pharmaceutical blister packaging. Firms are becoming aware of the cost value of using COC, and material disposal fees are an issue,” says Timothy Kneale, market development specialist, Topas Advanced Polymers Inc. (Florence, KY).

“The Topas COC 8007 F-04 grade has been the material of choice in classic drug blisters,” says Kneale.

Chemical resistance is an area of increasing interest in the healthcare industry. Unit packaging of alcohol-containing products, aggressive chemicals, and cements and adhesives used in medical procedures offers better dose control and safety but requires a chemical-resistant packaging system.

In a recent introduction, Tekni-Plex created a COC-based blister pack for peroxide-containing foam strips in the MetaTray and iWhite tooth whitening systems from Remedent. The application uses Tekniflex COC P15P co-extruded film with a 380-µm COC core layer, and polypropylene outer surfaces. An additional outer layer is a white polyethylene laminate (PP/COC/PP/LDPE) that protects the sponges from light. Completing the package, Tekni-Plex’s Teknilid WPSPPE peelable lidding contains a peroxide-resistant adhesive for sealing.

The COC film’s moisture barrier and chemical resistance allow extended shelf life despite exposure to the water-based gel with a peroxide content as high as 10%. Topas’s stiffness keeps users from pushing the sponge through the blister, says Kneale.

Tekni-Plex has also launched a line of high-barrier PETG/COC films in response to growing interest in clear moisture barrier packaging. In combination with PETG, Topas COC features a broad forming temperature range and performs well on standard thermoforming lines. “Topas is a transparent thermoformable barrier material. We are seeing its thermoformability add a lot of value right now where barrier must be maintained in applications with relatively deep thermoforming draw,” says Kneale.

For high-temperature applications such as in package sterilization, Topas 6013 F-04 is a high-temperature grade that withstands steam sterilization conditions of 121ºC. “High-temperature Topas grades can be used to create blister-based packaging that is resistant to boiling water and sterilization. You can autoclave a high-temperature grade COC laminate, and it will hold the blister dimensions without deforming, warping, or leaking,” Kneale says.