Protecting and Delivering the Ultimate in Wound Care
In 2009, Texas-based specialty pharmaceutical company ULURU Inc. introduced Altrazeal, a powder polymer material for treating chronic and acute wounds. When exposed to body fluids, the powder transforms into a three-dimensional microporous film that contours to the shapes of wounds. Capillaries form in the microporous film, promoting a high moisture-vapor transpiration rate, which helps manage wound exudate and creates an appropriate moist environment for wound healing. The film’s small pore size enables oxygen transport to the wound bed while preventing bacteria penetration.
The Packaging Challenge
Altrazeal has been recognized as an advancement in wound management. However, the formulation features an extremely low-density powder, making it exceedingly difficult to package in a manner that optimizes its presentation and application.
“Altrazeal is a very unique product. There is virtually no weight to this product,” observes Horst Boellmann, founder and chairman of Per-Fil Industries (www.per-fil.com), who has more than 50 years’ experience developing powder fillers. “It is one of the lightest products I have ever dealt with.”
|With the new blister package, doctors can easily control dosing of the wound care powder.
Altrazeal also requires barrier protection. “It is a hygroscopic product,” explains Angela Roggenhofer, sales and marketing manager of Tekni-Plex (www.tekni-plex.com).
When Altrazeal was introduced in 2009, ULURU employed 2-g and 5-g single-use foil-laminate pouches for sterility and moisture protection. But the pouches did not allow physicians to see the product or control product flow, making it difficult to apply without product waste. ULURU needed an alternative and sought the best-case scenario: a transparent blister package that sufficiently protected the product and greatly increased product control.
A “blister pack overcomes all the shortfalls of the previous pouch packaging,” says Kerry Gray, President & CEO of ULURU. Such a package:
• Avoids dust on opening the blister.
• Allows product to be seen during applications allowing easier dispensing.
• Includes a built-in spout applicator that provides an easy way to administer the product.
• Provides a more-appropriate volume for chronic wounds that makes the product more cost effective.
The challenge would be to fill a powder with a bulk density of 0.05—one whose notable flakiness drew comparisons to synthetic snow—consistently at a scant 0.75 grams. And the packaging needed to be moisture impermeable with a sufficiently strong seal.
Necessity Breeds Filling Innovation
ULURU decided to work with Tennessee-based contract packager A+ Secure Packaging LLC (www.apluspak.com), which had packaged Altrazeal’s veterinary product equivalent. To handle Altrazeal, A+ Secure Packaging needed a new filler that would be compatible with both blister thermoforming equipment and the product’s unique characteristics. Filling blisters individually by weight would be very expensive and, potentially, not commercially viable at high volumes.
An automatic filling system would need to accurately fill Altrazeal without changing the physical properties of the flakey powder. A+ Secure Packaging engaged filling machine manufacturer Per-Fil.
“Our purpose was not to alter [the physical properties of] Altrazeal,” says Per-Fil’s Boellmann. Conventional auger fillers, vacuum fillers, and compression fillers were considered, but Boellmann said a custom approach was needed. “We custom designed a system using rotary disc tooling and an air jet along with some components from vertical auger filling technology. The system gently sweeps product into a chamber cut into a round disc that moves between two plates. The air jet gently moves the product out of the chamber for dosing directly into a thermoformed blister.” To prevent the powder from becoming airborne and contaminating the sealing area and others, the filling system employs vacuum termination to accomplish air displacement, Boellmann adds.
Per-Fil tested the approach at its facility in NJ, making only minor modifications in the field. “Our dosing technology incorporating agitated powder densification allows the materials to be metered without compressing them,” he explains.
The Right Film for a Tricky Formulation
To find a film for the blister package, A+ worked with Tekni-Plex Inc., a global manufacturer of films and other value-added packaging products, to provide a solution offering moisture barrier and combatting static electricity induced by the powder during filling.
Tekni-Plex developed a sheet coextrusion process where a high-moisture-barrier cyclic olefin copolymer (COC) resin is combined with polypropylene “facing” layers, creating a symmetrical sheet capable of being thermoformed into blisters. “The beauty of COC film is that you can easily dial in the thickness of the COC and therefore the barrier,” says Roggenhofer.
Roggenhofer adds that she considered PCTFE, given its barrier performance, but the application also called for a deep blister, so “we needed a material that could form well in deep draws.” COC can be formed into large tray-like blister geometries, since its forming behavior guarantees even material distribution in the blister, which helps maintain the barrier and gives the package the necessary sturdiness during handling. “COC was the ideal material for the application because of its mechanical stability,” she adds.
For thermoforming, A+ Secure Packaging obtained a TF1e machine from Pharmaworks (www.pharmaworks.com). “We were approached for a machine that could form deeper blisters, so we provided the TF1e,” explains Ben Brower, vice president and sales director. The system “employs contact heating and accurate plug timing,” he adds. “A+ shared drawings of a 22-mm-deep blister, and we developed tooling with rounded corners.” Such a depth was “one of the deepest applications we’ve run on this model of machine,” he says.
The TF1e also offers superior cooling control, which “sets the material into the form of the blister,” says Brower. “We integrate active cooling with water running through the tooling, rather than using a cooling plate with tooling simply attached to it.”
Brower adds that his team wasn’t sure how the polypropylene would perform, “because it can act like a rubber band,” he says, so they were cautious. “But it ran really well. Good contact heating and cooling control were critical.”
The use of polypropylene as the outer layers of the structure did allow for easy adhesion to lidding stock. “We were able to provide our stock multilayer foil lidding, which seals well to polypropylene and peels cleanly,” explains Roggenhofer. “We did not want any flaking upon peeling open the blister.” The transparent COC also allows improved product visibility, while the lidstock is printable via inline technology.
Testing proved the blisters capable of withstanding the gamma radiation levels common to sterilization, needed for Altrazeal. “COC performs well after sterilization, so we thought polypropylene would be a challenge. We conducted sterilization trials in Europe and found only a very minor discoloration,” she reports.
The blister solution effectively eliminates all of the shortcomings of its foil-laminate pouch predecessor and reduces the treatment cost for small chronic wounds. Feedback from physicians showed that they greatly preferred the new blister packaging and, especially, its transparency and applicator-style design—both of which greatly assist in controlling powder flow.
“Both in the United States and internationally this packaging configuration is considered far superior to the previous foil pouch presentation,” says Gray. “It gives the product an innovative and high-tech image reflecting the major advance the product is in the field of wound care. Internationally, we now plan on launching a 2-gram blister pack as the market acceptance has been so favorable. On exhaustion of inventory we will also launch this pack in the U.S. market.”
ULURU was also pleased with the support of its partners. “We had very positive experiences with A+ Secure Packaging and were aware that they had expertise in this field, so to move forward with them was a simple decision. Per-Fil had prior experience with the product and was familiar with the challenges of filling this quantity. The first prototype of the blister was field tested and the comments received incorporated in the final blister design, including having individual blisters to avoid the sharp perforated edges of joint blister packs. Also having a larger blister volume to make it easier for the practitioner to handle and easier to fill.”
ULURU Inc. is a specialty pharmaceutical company focused on the development and commercialization of a portfolio of wound management and oral care products to provide patients and consumers improved clinical outcomes through the utilization of its innovative NanoFlex technology and OraDisc transmucosal delivery system. ULURU is headquartered in Addison, TX, and – through a network of strategic partners, licensees and distributors – is in the process of globally commercializing their product portfolio. For more information about ULURU, visit www.uluruinc.com.