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Science-based software and testing services expedite the material selection process and ensure blister packs deliver adequate barrier protection for solid-dosage forms without over-packaging.
Software and testing services streamline the traditional trial-and-error blister-pack design process to cut costs for manufacturers of solid-dosage forms and compress time to market. Eliminating expensive reiterations with a more automated design process ensures adequate barrier protection, maximizes shelf life, and eliminates over-packaging.
Klöckner Pentaplast’s BlisterPro XCEL suite of consulting, design, stability, and prototyping services makes it possible to develop prototype packages in two weeks. Housed at the new kp i.center in Charlottesville, VA, which opened in early 2015, BlisterPro XCEL design services have helped over 20 major pharmaceutical brands bring more than 50 solid-dose products to market more quickly and economically (1).
Other benefits include reduced materials waste and an uptick in overall productivity. “Speed-to-market, product safety, sustainability and cost control are essential factors in [pharmaceutical manufacturers] growing profitably around the globe,” stated Pierre Ferracci, group senior vice-president, Pharmaceutical Films Division, Klöckner Pentaplast (2).
“The kp i.center welcomes pharmaceutical developers from around the globe,” said Markus Pischulti, business director pharmaceutical films, Europe, Middle East, Africa (EMEA), noting, “The personalized experience isn’t limited to the facility in Virginia. The kp i.center team regularly exchanges ideas, designs and prototypes with groups in Europe, Asia, and beyond” (1).
BlisterPro XCEL’s services accelerate pharmaceutical product stability profiling through FreeThink Technology’s ASAPprime shelf-life modeling software and ASAP laboratory studies. FreeThink’s ASAPprime V4.0 integrates information about Klöckner Pentaplast’s Pentapharm film line to expedite selection of the most optimum barrier film for the product (2). At the kp i.center, modeling and simulation software such as finite element analysis allows designers to explore how a product fits into a proposed package concept and compare design iterations. Designers also use it to examine how different polymers influence performance and how various geometries impact stability and barrier properties. The kp i.center also can perform physical buckling or crush tests to determine how a package performs under load, where deflection occurs, and locate weak points that compromise shelf life. Drop testing validates end-use package performance (3).
“We have CNC [computerized numerical control] equipment to make tooling and an Uhlmann blister line to run prototypes,” Michael Rashed, senior manager, Global Marketing, Pharmaceutical Films Division, Klöckner Pentaplast, told Pharmaceutical Technology in an interview at PACK EXPO Las Vegas (September 28–30, 2015). “That way package development doesn’t slow down in-house production lines. We can even model the distribution chain,” he said.
Package optimization help also is available from Allied Development, which recently added SavvyPack Barrier Assistant to its SavvyPack Analytical Services, a toolbox of integrated value chain, lifecycle, and barrier analysis services. With a database of permeability data for all packaging materials, SavvyPack Barrier Assistant calculates the permeability of any blister structure. Adjusting for thickness, temperature, and humidity allows structures to be optimized without time-consuming and expensive physical testing (4).
According to Bilcare Research, many major pharmaceutical companies rely on its BilcareOptima service. Available worldwide, it’s been used in Europe, Asia, and North America. In an interview with Pharmaceutical Technology, Ajith Nair, PhD, senior vice-president of Research & Quality at Bilcare Research, said, “Tests that determine the optimum blister film barrier properties for packaging certain pharmaceutical products can take as little as 15 business days. Expedited drug stability tests help overcome the time and resource crunch [that] packaging engineers and formulators of global pharmaceutical companies face when attempting to achieve successful stability studies. The vast majority of packaging-related stability failures can be ascertained by systematically analyzing the product’s physical attributes, as opposed to more stringent, time-consuming chemical testing.”
Bilcare’s 15-day FastPack process determines a product’s susceptibility to environmental factors such as humidity, temperature, light, and oxygen, through scientifically designed experiments. To ensure accurate results, three batches are tested. Forced degradation testing examines product characteristics such as hygroscopicity, physical degradation, chemical degradation, drug-release properties, hardness and friability, gas liberation, and material/product interaction. Test data identify threshold values and optimum barrier and help optimize material selection.
Bilcare designs the ideal blister cavity using SolidWorks 3D Software and simulates cavity thinning and moisture permeation through finite element analysis software (5). In addition to blister cavity drawing and permeability data, the FastPack process provides a packaging cost analysis with material specifications and testing methods, plus samples of recommended packaging materials.
The FastPack process is based on research findings from Bilcare’s BilcareOptima, a scientific packaging development and sensitivity profiling method following quality-by-design principles. Nair said, “It has proved not only sufficient in identifying a product’s optimal packaging materials in terms of cost and barrier protection, but also in yielding a greater than 90% certainty of passing a packaging stability study. For pharmaceutical manufacturers, this means reduced risk of both FDA approval delays due to insufficient package barrier properties and, conversely, wasteful and costly over-packaging.”
The process enables market launch in optimized packaging, saves development time and cost, provides complete understanding of the product’s sensitivity, simplifies the design of additional packaging structures for specific climatic conditions, identifies stability issues, and documents packaging development (5).
Simulating stress and cross-permeation
For cold-formed foil blisters, Constantia Flexibles offers Live Stress Check and Cross-Permeation Simulation (see Figure 1). “Both services are optimal tools to reduce the cost and resources associated with trial-and-error development,” Cora Helberg, marketing and innovation manager, Pharma Division, Constantia Flexibles, said in an interview with Pharmaceutical Technology.
The Constantia Live Stress Check tool determines the strain level applied to coldform foil and examines the quality of the forming process. Results are used to optimize the mechanical forming process by showing potential improvements in forming plug designs, plug materials, and process setup (6). Helberg said, “Live Stress Check can be used for different reasons: qualification of new tools; qualification of the coldforming process in the blister line; troubleshooting; basis for blister size optimization; [or] choosing the right material for a given blister shape or production process.”
To perform the stress check, a pattern of high-resolution dots is printed on the Coldform laminate. The sample is run on the blister machine and inspected with a camera system and special software to identify areas where dots are distorted. An automatically generated, three-dimensional image illustrates the degree of strain on the blister. With this information, adjustments can be made to the process and cavity-shaping tooling (6).
The Cross-Permeation Simulation determines the level of moisture and oxygen ingress along the seam between the two laminate layers. Such cross-permeation can be controlled by matching the inner layer of the laminate to the barrier needs of the product. For example, for more sensitive products, higher barrier polypropylene can replace a polyvinyl chloride layer.
Cross-permeation also can be influenced by the blister’s design. Reducing cross-permeation may involve adjusting the sealing area or eliminating blister perforations altogether. Helberg explained, “If the clients know how sensitive their products are, with Cross-Permeation Simulation we are able to give a prediction about the likelihood of a success in the stability test. The method can also be used to identify reasons for shelf-life problems.”
Another potential aid to blister material optimization is in-house permeation testing. It can be done on equipment from MOCON. Ten times more sensitive than the model it replaces, MOCON’s OX-TRAN Model 2/22 L tester quickly measures oxygen permeation down to 0.005 cc/(m2•day) at precise temperature and relative humidity (RH) conditions. When testing film with unknown characteristics, an auto-test feature determines the optimal parameters and conducts the test to completion.
Automatic sequential testing supports situations where materials need to be tested at various RH and temperature levels. This feature allows the operator to establish up to 10 different RH and temperature conditions in a single test setup, and then automatically run all tests without further operator input. Changes from wet to dry testing can be done with a click, reducing setup and testing time because operators don’t need to empty the reservoir or wait for the system to dry.
A gas-saver feature automatically reduces consumption when the system is idle. An install wizard and intuitive touch screen simplify setup and operation. Connectivity options provide remote viewing and control from anywhere in the world. The unit also eliminates several common maintenance expenses and adds safety features to increase component lifetime.
For companies that prefer to outsource testing, MOCON’s Consulting & Testing Services Group provides standard and advanced permeation testing services. Its global network of labs in Minnesota, Texas, Colorado, Germany, China, Canada, Australia, Switzerland, Poland, India, and the United Kingdom was joined by Life Pack Labs in Vista, CA. A business partnership between MOCON and Life Packaging Technology LLC, Life Pack Labs is dedicated to meeting the packaging design and validation requirements of pharmaceutical and medical-device products (7, 8). Testing is done in accordance with international standards and includes calculation of permeation rates for water vapor, carbon dioxide, and oxygen and measurements for attributes like film thickness, flex strength, and package integrity (8).
1. Klöckner Pentaplast, “Klöckner Pentaplast at Pharmapack Europe Exploring BlisterPro XCEL Suite of Services,” News Release, Feb. 1, 2016.
2. Klöckner Pentaplast, “Klöckner Pentaplast Pharmaceutical Films Division Adds Product Shelf Life Modeling to BlisterPro XCEL Package Design and Prototyping Services,” News Release, Sept. 28, 2015.
3. Klöckner Pentaplast, “Klöckner Pentaplast Design Services,” News Release, Sept. 28, 2015.
4. Allied Development “SavvyPack, We Are Proud to Introduce a New Feature–the Savvy Pack Barrier Assistant,” Email, Nov. 5, 2015.
5. Bilcare Research, “BilcareOptima,” accessed Feb. 25, 2016.
6. Constantia Flexibles, “Constantia Flexibles Introduces Live Stress Check and Cross-Permeation Simulation for Constantia Coldform,” News Release, Jan. 14, 2016.
7. MOCON, Inc., “Life Pack Labs Open for Business; Offers Package Development, Testing for Pharma, Medical Devices,” News Release, Oct. 13, 2015.
8. MOCON, Inc., “Standard Permeation Rate Testing,” accessed Feb. 29, 2016.
Article DetailsPharmaceutical Technology
Vol. 40, No. 4
When referring to this article, please cite it as H. Forcinio, "Blister Pack Optimization," Pharmaceutical Technology 40 (4) 2016.