SubscribeSave time and tools through virtual design of formed blisters.
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 realising 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. In fact, this approach is now so well accepted, that no actual prototypes are built, until the design and simulation work is completed. This has significantly shortened the development time between each new model launch, against a backdrop of ever increasing legal requirements related to passenger and pedestrian safety.
The pharmaceutical packaging industry faces similar challenges, and it could very well benefit from the same solution. Pharmaceutical companies have already turned to virtual modelling 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.
REVOUTION 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 visualise the appearance of a tablet in a package.
Figure One. Prediction of final shape and thickness of individual blister
Some very recent studies using such modelling have shown that, in an extreme example, changing the shape of the pill and the cavity can change barrier of a thermoform by 400% (see Figure 1) and small changes in the draught angle, radius, chamfer, and surface finish can lead to pin holing in a cold form blister.
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.
VIRTUAL DESIGNS
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 mould. 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 plug can then be designed to assist the forming of the cold form or thermoform blister.
Figure Two. Cubic and Hemispherical Virtual Tools
A range of packaging materials can then be selected for performance assessment on these tools. Using extremely specialised 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 laid onto the virtual mould can 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 for thermoform blisters, and plug speed, and plug slip for cold form blisters. This simulation builds up a unique topography of the gauge distribution within this virtual pocket. From this it is possible to check that the material has not been stretched beyond a specified limit for pinhole development for cold form; or the thickness can be integrated to give the moisture barrier for that combination of material, cavity, and forming conditions, for thermoform materials
A range of material 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 optimised 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 thermoform blisters, and the confirmation that the elongation does not exceed the limit to prevent pin holing. 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.