Simulating Blister Design
Save time and tools through virtual design of formed blisters.
by Nic Hunt
Global Business Director, Rexam Pharma Flexibles and Rexam Pharma Services (Bristol, England)
|Figure 1. Cubic and Hemispherical Virtual Tools. The cube has a volume of 2.00 ¥ 10–6 m3 and a barrier of 0.0006 g/m2/day. The hemisphere has a volume of 2.01 ¥ 10–6 and a barrier of 0.00015..|
The pharmaceutical industry can learn a lot by looking to the automobile industry, which has had to perform crash and safety testing on all new models for many years. Historically, that industry used to make near-production models, crash test them, and repeat the processes several times until success. After realizing that this approach slowed new product launches, the automobile industry began using computer simulation to reduce the number of iterations, crashing virtual cars up until the final models and reducing the development cycle to meet business targets.
The pharmaceutical packaging industry faces similar challenges, and it could very well benefit from the same solution. Pharmaceutical companies have already turned to virtual modeling systems to develop new molecules and can now predict synthesis routes before going to the lab. And now pharmaceutical packaging professionals can transfer this process to the development of drug packaging.
All throughout its development, a drug has to be evaluated in its package, which can make successes or failures out of stability trials. In the past 25 years, significant expertise has been developed in blister materials selection, performance, and quality, but all of this focuses on rolls of flat material. That's fine, except that no drug is packaged in flat material. It goes into a blister cavity that protects the tablet. Instead, simulating that cavity may give packagers the opportunity to evaluate carefully the formed shape before any tools are made.
REVOLUTION IN DESIGN
Systems can now predict the performance of a formed blister pocket without leaving the virtual world. They can calculate the thickness of every part of the barrier film as it transitions from a flat sheet to a formed blister. At that point, barrier to light, moisture, or gas, and mechanical properties such as crush strength or rigidity, can be calculated. Simulation can also help packagers visualize the appearance of a tablet in a package.
Some very recent studies using such modeling have shown that, in an extreme example, changing the shape of the pill and the cavity can change barrier by 400% (see Figure 1) and small changes in the draught angle, radius, chamfer, and surface finish can change barrier by up to 40%.
Should this matter? Of course. A bad tool can negate good materials selection and can delay a launch. New drug and cavity shapes (perhaps changed by marketing in Phase III) might not match the performance of the ones used initially, leading to product failure and redesign of materials or tools. Tooling and conditions on the production unit could differ from those on preproduction units, leading to product recalls.
How does this type of simulation work? Based on compression drawings of the tablet, a 3D virtual pill is drawn. Around this, a cavity is made that will hold the pill and meet requirements such as headspace. The fit of these can then be checked in 3D. This becomes a virtual mold. It can be rotated, angled, and viewed in true 3D, just like a metal tool. In the virtual world, it has hard surfaces with the same strength and slip characteristics as a tool.
A range of packaging materials can then be selected for performance assessment on these tools. Using extremely specialized equipment, the mechanical performance of these materials at forming conditions has been predetermined. The data enables the creation of a virtual version of each film. Each material can be layed onto the virtual mold and thermoformed. Since all machines are different, the forming conditions can be varied in the virtual world. Typically, variables are temperature of the web, air pressure, and forming time. This simulation builds up a unique topography of the gauge distribution within this virtual pocket. This can be integrated to give the theoretical barrier for that combination of material, cavity, and forming conditions.
A range of materials will give a range of pocket barriers. These are generated as discrete numbers, enabling direct comparison of different materials. Also, virtual tools can be changed quickly, and materials recalculated to assess improvements. Different tablet shapes with the same active levels can be evaluated.
When an optimized cavity shape is produced, the true 3D shape can be captured in the format compatible with CNC equipment to give a truly repeatable drawing for all future tools. It can be captured as a data file, negating the need for a partially dimensioned cavity drawing. It then can be cut as a tool and run for packaging trials. Since the thickness of the material has already been calculated, the machine's setup during the trial can be assessed by comparing the actual thickness of the product versus the theoretical thickness.
The advantages are that metal is not cut for tooling and initial packaging machine trials or laboratory tests are not needed. All the elements of the virtual world can be fully quantified and dimensioned. Changes and ideas can be made quickly, and the output for a range of materials can be assessed the same day. But most importantly, simulation generates data numbers for the barrier to moisture, gas, and light for an individual cavity. If you change shape, you have a benchmark on performance. If you change climatic zone, the needed barrier increase is already known, so packaging upgrades can be estimated. And if you change a marketed product's barrier by cavity design, this needs only be noted in an annual report to FDA, because tooling is not a product contact material. A change in materials is not always so simple.