Medical Device Link.

Blister Packaging Materials

Nic Hunt, global product director, Rexam Medical Packaging (Bristol, United Kingdom)

To select the best material combination for their blister package, drug packagers should understand how raw blister materials are formed in order to process them successfully. Until recently, blister packaging requirements, such as processability and resistance to moisture, light, and oxygen, have been satisfied with a small range of products. However, several new barrier materials and material combinations have been used in recent years that differ in their functional performance, especially in terms of moisture barrier, and are flexible enough to run interchangeably on most packaging machinery.

THERMOFORMABLE MATERIALS

Monolayer PVC, duplex PVC/PVdC, triplex PVC/PE/ PVdC, and PVC/Aclar laminates can all be converted into blister packaging by thermoforming.

Monolayer PVC is produced by a calendering process using PVC resin. An extrusion screw melts and homogenizes the PVC resin, during which any necessary additives can be incorporated. The melt, at this stage more than 10 mm thick, is then thinned to the correct gauge and width using a calender stack, followed by a film-forming stack. The PVC film gauge, critical for both coating and lamination, is controlled to ensure a uniform thickness and a minimum spot gauge variation. Monolayer PVC used for blisters is typically 190–300 µm (7½–15 mil) thick. It is commonly used for applications that require little moisture barrier, but where cost and processability are critical.

The most commonly used barrier material is PVdC. In its pure state, PVdC is similar to glass—it has an extremely high barrier but is very brittle. To overcome this, processors copolymerize the vinylidene chloride monomer with members of the acrylic family. The exact acrylic used, and the quantity in the blend, can be chosen to achieve certain properties. PVdC cannot be used as a mono film because of its relatively high cost and its mechanical properties.

Blending, however, does affect PVdC's barrier qualities. Processors can make it flexible and soft by adding high levels of a comonomer, but this lowers the overall percentage of VdC and reduces its barrier. Adding a high-barrier alternative produces a hard coating, which helps the material flow through the packaging machine, but shortens its life in roll form because of its brittleness. Only by mixing coatings can the optimum levels of performance be achieved. The best option is to combine the PVdC with a layer of PVC. Different coating methods result in different barrier levels, because the different methods lend themselves to different copolymers.

There are three main ways to apply PVdC to PVC: aqueous coating, lamination, and extrusion coating. Currently, the industry applies PVdC to PVC from an aqueous emulsion using reverse-roll coating.

By using a coating roller engraved or grooved with a known and consistent pattern, processors can maintain precise control of the coating weight. The size and shape of these grooves can be equated mathematically to a fixed quantity of coating. As the coating machine runs, the cylinder's surface is scraped clean with a doctor blade, leaving only the coating-filled grooves. The coating, which is approximately 50% PVdC and 50% water, is then transferred onto the PVC web. The coating is then allowed to dry. Several layers are applied to achieve the correct barrier, which usually has a total coating weight of 20–180 grams/m².

Even though PVdC is the oldest thermoformable barrier blister material, it is not the only material widely used. Aclar films, developed by AlliedSignal (Morristown, NJ) a number of years ago, are also used as barrier materials in blisters. Aclar is a polychlorotrifluoroethylene polymer, but, unlike PVdC, is not applied through coating but through lamination. It is from the PTFE family and as such offers similar properties. PTFE possesses a chemical structure in which the atoms form a unique regular helical structure. It has no easily accessible sites for reaction to take place; hence, little sticks to it. Aclar possesses many of the same properties.

Aclar is initially produced in solid granular form, which can be extruded into a monolayer film. In this state, it provides excellent barrier, but at the thickness required for a mechanically sound blister pack, it is too costly and offers excessive barrier. To convert it into a form with the correct barrier and reasonable cost, Aclar is laminated to either PVC or PVC/PE film. During lamination, an aqueous adhesive is applied to the PVC web, then dried to make the surface tacky. Aclar is then introduced to the adhesive and compressed or nipped to laminate it to the PVC. Careful control of the drying and line speed, as well as the use of various components within the adhesive, ensure the consistency of the finished product.

COLD-FORMABLE MATERIALS

Cold-form products rely on a layer of deformable aluminum to impart barrier to the blister pack. As a monolayer, aluminum has traditionally been prone to cracking during the forming process, which has limited its performance. To overcome this, processors laminate it in a sandwich of PVC or polypropylene and biaxially oriented nylon or oriented polyamide (OPA). Individually, the layers perform the following functions:

• The OPA or nylon acts as the mechanical layer in the structure. It has a higher mechanical resistance than the aluminum.

• The aluminum acts as the barrier layer. Aluminum is the ultimate barrier to moisture, gas, light, and flavor.

• The PVC or polypropylene layer acts in two ways: it seals well to lacquered foils, and it is inert. It also acts as a bulking layer to increase the overall weight of the product.

NEW MATERIALS

Several new barrier materials have been launched in recent years. Aclar CX 130E has been developed based on the success of the standard Aclar. It uses multilayer technology to support a much thinner layer of Aclar in a sandwich structure. This material offers less barrier than the standard Aclar with a comparably reduced cost. The material is still laminated to either PVC or polypropylene to provide the required mechanical and physical properties and will have moisture barrier of 0.78 g/m²/day at 38°C and 90% relative humidity.

Developed using the new catalyst systems that give much greater control to polymer formation, the new cyclic olefin copolymers offer very high moisture barriers while being totally polyolefinic.

Polypropylene has been used for blister packaging for several years, although processors have faced some challenges. However, modifications to the blister packaging line can enhance the line's performance to manage the characteristics of polypropylene. In the future it may be possible to use advanced analytical processes to develop polypropylenes that can run on more-conventional machinery.

The interest in alternative materials is growing, yet pharmaceutical companies are reluctant to switch because it entails substantial cost and production time to development them. To reduce development costs, some packaging companies are using computer-aided design and analytical equipment to mimic forming conditions in a controlled, measurable environment. Figures can be generated for a range of test polymers and at specific parameters, and this data can be used to predict whether a material can be thermoformed on specific machines. Use of such a system can reduce trial and error, and therefore help save money and time.