Medical Device Link.

BLISTERS

Klöckner Pentaplast (Gordonsville, VA) is offering the Pentapharm BlisterPro blister design software for finite-element modeling of thermoformed drug blister packages. The software provides estimates of thickness distribution, surface area, and permeability for CAD-simulated cavities. Engineers can design optimal blisters around product shapes and barrier requirements, exploring the effects of tool geometry, film types, and process conditions before running actual tests.

Many factors influence the choice of materials for blister packaging. Drug manufacturers have sought blister clarity to support customer use and product merchandising. Sensitive drugs need barrier protection, while others require cost-effective materials.

Today’s materials have met many needs. PVC/PVdC-coated films, as well as laminates incorporating Aclar and COC, address barrier requirements. For drugs with moderate barrier needs, PVC offers favorable forming and sealing characteristics at a lower cost. Foil laminates protect against moisture, oxygen, and light.

The selection of blister materials in some cases is driven by company preferences for certain package styles. “Companies’ blister material choices are sometimes based on aesthetics and what they are used to. There are companies that like foil, and companies that don’t,” says Remco Van Weeren, senior vice president of films and foils, United States, Bilcare Inc. (Phoenixville, PA). “In a lot of applications, companies end up using a higher-barrier package than what is really needed,” he adds.

The cost of making foil blisters and investing in cold forming technology has inhibited the wider deployment of foil materials for blister packaging, says Robert Hartwig, managing partner, BTS International (Franklin Lakes, NJ), and manager of North American operations for Rohrer AG (Mohlin, Switzerland). “Aluminum has always been more expensive, because you have to use more material. As such, it has been a kind of solution of last resort,” Hartwig says.

“There are 400 to 500 medium-to-large thermoformers doing production work in North America. Of these, 50 to 70 can run aluminum. For foil production, thermoformers would have to bring in new machines or retrofit old machines, which is expensive and sometimes impossible,” says Hartwig.

But advances in foil processes may make naysayers take a second look. Rohrer AG has introduced in the U.S. market its High-Pressure Cold-Forming (HPC) technology. HPC reduces material and related costs associated with traditional blister cold forming. The HPC system incorporates a two-step forming process into one dedicated tool that supports efficient retrofitting of thermoforming and traditional cold forming machines.

“We can put almost as many blisters on a card as with thermoformed film. This technology enables the use of much less aluminum to make the cavities, as well as smaller blister cards, which require much less secondary and tertiary packaging,” says Hartwig.

SHRINKING FOIL CARDS

The HPC technique creates blisters with the steep walls and rounded bottoms of thermoformed cavities, allowing a 20% reduction in blister card size. “You can produce more cards per cycle, so you avoid the penalty of a 30–50% drop in output when you switch from thermoform to cold form,” Hartwig says.

Hartwig says Rohrer’s single-tool configuration improves on Advanced Forming Technology, a system introduced some years ago by Romaco/ Noack, which reduces blister card size but requires two forming stations.

“Advanced Forming Technology was a nice idea, but wasn’t a practical retrofitting solution, because it used two forming stations. We can retrofit HPC to a host of existing machines and easily exchange tooling for HPC, traditional cold forming, and thermoforming. This can generally be done on the customer’s floor, saving time and taking out half the expense,” he says.

The first portion of the cavity is preformed with a traditional plug. While the laminate is still clamped, high-pressure air is introduced to conform the material to a preformed female cavity.

“This is not unlike plug assist normally used in thermoforming, but the air blow is 40 to 60 bar, compared with 5 to 6 bar used in plug assist,” Hartwig says.

Rohrer AG’s High-Pressure Cold-Forming solution forms steep-walled foil cavities, allowing a 20% reduction in blister card size.

Proprietary cavity-modeling software, developed with the Swiss Federal Institute of Technology (Zurich), is used for mold configuration and testing of foil materials. Rohrer has demonstrated pinhole-free cavity formation designing blisters with foil films from Alcan Packaging, Alcoa, and Hueck. “The process should work for 90% of the foils commercially available,” he says.

Rohrer will open a facility in the Northeast in the first quarter of 2007 for selling Rohrer HPC form-fill-seal units and the aftermarket tooling. “We are bringing this solution very cautiously into the United States. In the last year, we have started trials and studies with several major pharmaceutical companies that would adopt HPC for new drug launches,” says Hartwig.

Rohrer is working with equipment manufacturers for packaging quick-dissolve tabs and delivery systems such as orally dissolvable films and transdermal devices. A partnership with Harro Hofliger has focused on inhalation-delivery applications. “Using HPC, we can provide even distribution of the aluminum, and smaller cavities with very specific cavity geometry for creating the airflow necessary to get the powder out of the cavity,” he says.

Van Weeren sees the technology as “potentially encroaching on higher-barrier film materials. There is a potential of limiting the cost differential with film, where total foil cost could approach that of film,” he says.

Paul Glintenkamp, director of pharmaceutical packaging, Carton Service Inc.—Packaging Insights (Norris, TN), also sees an opportunity for cost savings. “In typical cold forming, you can’t have as many blisters in the same index, and you also have to run slower, so you don’t fracture the form. A reduction in blister card size from 20 to 30% would certainly relate to material and production cost savings and increased production output. For instance, you might be able to run six up in a cycle instead of four up. If you are running millions of blisters, [the HPC technique] could put cold forming costs on a par with thermoforming,” Glintenkamp says.

Package revalidation would be less onerous for companies already packaging a product with foil. “A retrofit would require process revalidation. I believe a company could use accelerated stability testing on the packaging, because they are staying with the same material, but in a different format and cavity size, which would be smaller. Since the cavity size is smaller, the opportunity for success is very strong,” he says.

Victor Gherdan, manager, package design engineering, Cardinal Health Inc. (Philadelphia), says the technology promises several advantages. “Reducing the size of the cold-form unit-dose package has been the goal for many years. The industry is not using the material as efficiently as it might in traditional cold-forming systems,” Gherdan says.

STANDING UP TO FILM

“There are many potential benefits to the HPC solution. You are reducing the overall size of the blister package. The cost savings from using less material is evident, but this also opens up opportunities to run certain-size blister units that have not previously been possible. Monthly regimens of 28 to 30 pills become almost impossible to produce with traditional cold forming. This has required packaging the pills in strips and the use of secondary blister cards,” Gherdan says. By forming cavities closer to the size of the pill, the risk of double filling is reduced, along with the need for dedicated feeding systems. “There could also be opportunities for creating complex foil cavity shapes, with deeper draws for packaging liquids and creams,” he says.

Gherdan notes that unit cell size is to some extent dictated by printing requirements. Foil blister footprints might have to be larger to accommodate graphics that can’t be printed on the formed side as with thermoformed blisters.

The new cold-forming technology HPC, developed by Rohrer AG, works in two steps. In step one, the cavity is mechanically preformed. In step two, final forming is achieved through the use of high pressure. (click image to enlarge)

Rohrer tested the process with Alcoa’s Cold Form 3000 foil laminate to draw blisters to deep-formed cavities with 60-degree-radius walls, says William Sharpless, global marketing director, Alcoa Flexible Packaging (Richmond, VA).

“In comparing the economics of cold forming with thermoforming, you must focus on the material yield per cost of 1000 sq in. as well as the rate of equipment output. If one can put eight cavities instead of four on a blister, an alu-alu structure will compete better with a thermoformed blister. You can utilize flood feeding, which greatly decreases overall machine cost. With these combined advantages, we believe this technology can increase the use of cold forming in the market,” says Sharpless.

Rohrer will have to demonstrate the solution’s practical value and the integrity of the foil blisters, say packagers. “The HPC process has to be proven in practice to be just as reliable if not even better than current systems, without sacrificing cycle times and production rates. It has to be cost-effective to adopt. We have several form-fill-seal lines and redundant capabilities on-site, so the cost of retrofitting would be a very important consideration,” says Gherdan.

“As a contract packager, we would want to implement the technology without sacrificing the capabilities we currently have. So we would need tool change capability to convert retrofitted machines back to traditional cold forming and thermoforming. It is not clear to us whether they can actually do that,” Gherdan says.

Cardinal Health would require adaptability for running many different laminates. Tool cost and tool design turnaround time also have to be considered, since Rohrer is building the forming tool with its proprietary software. With in-house control on package design, Cardinal Health design engineers can quickly develop custom blister and package designs to meet customers’ time requirements. The Uhlmann UPS-4MT is the packager’s predominante cold-forming unit.

“Our customers don’t like to wait too long. It would be critical to have quick turnaround time on the initial design,” Gherdan says.

Says Glintenkamp, “We would want to see engineering studies first, with accelerated stability results as well, that demonstrate acceptance ranges and failure rates, and prove that the process doesn’t fracture the foil as you increase the incline and production rates,” he says.

Bilcare is promoting Nova, a coated-paper lid stock material, as a low-cost alternative to foil lidding for PVC blister packages. Van Weeren says that foil lidding is often an unnecessary expense for packaging with limited barrier needs. “A package using PVC with Nova paper lidding provides a comparable barrier to a PVC blister with foil lidding,” he says.

STABILITY TESTING

The U.S. division of Bilcare supplies rollstock foil laminates, PVC, and PVC/PVdC coated films. “We are a broad-portfolio supplier of materials. Some materials are developed specifically based on customers’ requests, and we are supporting package redesign development to support customers’ barrier and branding requirements,” says Van Weeren.

Bilcare has introduced a new product stability testing technology. By first testing the product stability characteristics without the packaging material, firms can optimize their choice of packaging to ensure stability with the most cost-effective material, says Van Weeren. “Typically, companies put product up on stability using multiple materials, without a good understanding of the nature and stability profile of the actual product. We run a testing protocol that examines the product without the packaging, testing for a wide variety of chemical and physical properties. You derive a much better understanding of the product, and the humidity and temperature levels that affect its characteristics,” he says.

“We have found that pharmaceutical companies are similarly more focused today on product stability testing. They understand the limitations of current package stability testing that often lead to longer development times and more costly packaging than is necessary,” Van Weeren says.

FRIENDLY AND SAFE

Cardinal Health has developed a new child-resistant (CR), senior friendly (SF) fold-over blister package design that recently earned an F-1 rating from the Consumer Product Safety Commission.
The HingePak is composed of a blister unit sandwiched between multiple layers of paperboard. The configuration employs three sequences to dispense a pill.

“This is the first CR adult-friendly blister package that has gained an F-1 rating and that is very simple to manufacture. It doesn’t require special equipment or components. The unique HingePak design adds another CR, SF package, with the highest CR rating, to our portfolio,” says Gherdan.

The package features a sliding gate component, formed with an internal paperboard layer, that controls access to the individual doses. The user presses a thumb on a perforated tab on the back of the blister card to create a protrusion on the front of the card that sets the sliding gate in motion. The card is flipped over, and the user slips the sliding gate away from the product cavity. Then the product is pressed out through the back of the card.

Cardinal Health is testing a COC laminate for use on a CR, SF blister with a unique tear-open feature, incorporated into the forming web. “We are working with Tekni-Plex and Topas in evaluating the COC laminate’s mechanical properties. We are interested in COC’s capacity for controlled tearing, puncture resistance, and improved thermoforming.”

For dispensing an animal healthcare product, Cardinal has developed a patent-pending dual-chamber cold-form blister that keeps two ingredients separate until application. The user pulls a tab to rupture the ends of two pipettes extruding from two separate cavities. Liquid is released in a single motion when the user folds the blister unit in half and simultaneously squeezes both cavities.

Alcoa’s Safety-Pak Plus lidding material supports CR and senior-friendly OTC and Rx blister packaging. The product employs a PET/foil laminate with a release adhesive that is easier to remove than paper-based lidding. The user pulls back the poly film to expose the foil. The mechanism provides greater lidding adherence, and the dwell time is shorter in processing. Moisture, which can be absorbed by paper, can lead to blistering or delamination after high-speed blister production, or poor material storage. “With Safety-Pak Plus, this is eliminated,” says Sharpless.

In addition to a traditional peel-push structure, the product can be configured so the foil and PET peel off together to expose the doses. “This is an attractive feature for the European market, where they use opaque blisters instead of peel-push for the CR feature. It adds CR value, because children can’t push through it,” he says.

In another application, Alcoa can produce a Safety-Pak Plus laminate with a bond strength that resists peeling altogether. “We are working with a pharmaceutical company, calling this a “lock-tight” mechanism. The patient would use a tool to open the package. This could possibly qualify as an F-1 blister,” Sharpless says.

BARRIER FILMS PROGRESS

INEOS (Lyndhurst, UK), parent company of INEOS Films, specializes in the manufacture of pharmaceutical blister packaging films, with facilities located in Germany and India. A new INEOS Films Pharma Films facility is scheduled to open in Delaware City, DE, says commercial engineer Todd Swartz, INEOS Films (Grand Rapids, MI). The company makes mono-PVC, triplex and duplex PVdC-coated films, and Aclar/PVC laminations. It gained the capability of manufacturing Barex resin with its acquisition of BP INNOVENE, the resin’s sole producer, says Swartz.

INEOS Films’ Aclar/PVC materials lie flat, which eliminates the common tablet-feeding and blister-to-carton-feeding issues that occur with typical Aclar/PVC laminations, says Swartz. “Aclar shrinks in the transverse direction and grows in the machine direction, whereas PVC is designed to shrink in the machine direction. This relationship creates many issues with some Aclar/PVC laminations,” says Swartz.

The laminations minimize the stress that occurs in the lamination bond to reduce the curl effect and provide “easy form” characteristics. “Our material processes at temperatures that are more common to mono-film PVC thermoforming. This enables customers to use wider and more-forgiving equipment process parameters,” he says.

Another strategic INEOS Films’ material is its line of PVdC structures.

A proprietary PVdC-coating line uses strict process controls to produce PVC/PVdC films with coating weights of 40, 60, 90, and 120 g/m².

“Our duplex structures meet or exceed the barrier offered by traditional triplex specifications that employ a polyethylene (PE) layer. The PE layer has no barrier value. By eliminating the PE in the heavier coat-weight PVdC structures, we have eliminated the material cost of the petroleum-based PE and the cost of labor in PE application.” says Swartz.