Blister packages made of macromolecule polymer materials have increasing application in the market. In drug packages made of macromolecule polymer materials, there is an overall trend that containers are being replaced by composite flexible packages. Nowadays, polymer materials used in flexible drug packages are developing rapidly. As new materials keep emerging and people’s understanding of them keeps improving, polymer materials continue to upgrade. For example, PVC, a blister flexible package forming material widely used in the market now is an amorphous high-molecular polymer. Its main feature during processing and application is that it has no obvious melting point and becomes plastic when heated to 120-150 °C. However, due to its poor thermal stability, alkaline stabilizer has to be added to neutralize hydrogen chloride in order to inhibit its autocatalytic cleavage reaction. On the whole, PVC features chemical resistance, wear resistance, flame resistance, self-extinguishing, high strength, electric insulation, barrier property, low price and wide source. PVC films used in drug blister packages are made of PVC resins with addition of some processing agent and extruded and calendared to produce products in line with requirements for medical use. As forming material of blister package, PVC plates can separate individual tablets, pills and capsules into minimum package unit to greatly enhance accuracy and safety of drug using. Since such processing method is simple with low investment and easy processing, it helps cut production cost of pharmaceutical companies and significantly improve production efficiency. Since the beginning of its application until now, most pharmaceutical companies use it to pack tablets, pills and capsules.
Until 1990s, original PVC film-packed drugs were found to be poor in water vapor barrier property, thus unsuitable for packing drugs with requirements for resistance to moisture and vapor. In particular, pills, powders and granules in traditional Chinese medicine have higher requirements for resistance to water vapor and moisture; therefore, packing materials should be selected with more care. Moreover, people learn from long-term processing and use of PVC that it has negative impact on human living environment and living organisms. When PVC polymerizes monomers, it produce VCM; when PVC products are burnt, dioxin hydrochloride will be produced; when PVC decomposes, hydrogen chloride produced will pollute the environment and relevant monomers, plasticizer and stabilizer have serious impact on human body and the environment. In developed countries, such as Germany, pharmaceutical companies have stopped using PVC in blister packages; in Japan, limits have been imposed on production of PVC products. As PVC as a material for blister package is about to be replaced, it is imperative to select a new high-molecular polymer as blister packing material to ensure usability and safety of drugs.
1. High-barrier new high polymer material for drug blister package
1.1 PVDC
PVDC usually refers to copolymers with VDC as main component. In PVDC used in drug blister packages, the content of VDC is around 90% and other monomers such as acrylic acid and acrylic ester are most frequently used VDCs. Such comonomers serve as internal plasticizer to improve PVDC processing performance without greatly compromising its barrier property. PVDC processing began in 1930s when DOW in U.S. started PVDC industrial production for the first time. It was at the time of the Second World War when PVDC was mainly used in packing military products. Later, as world industry developed rapidly, exceptionally excellent performance of PVDC in quality guarantee for foods and drugs and in extending their shelf life stood out. After that, PVDC’s dominant position as a high-barrier material has never been challenged for decades. PVDC has large high-molecular density, regular structure and high crystallinity, thence it possesses excellent air tightness and resistance to moisture, oil, chemicals and solvent. Due to copolymerization modification, PVDC is suitable for both coextru-lamination and membrane blowing to facilitate compositization with other materials to form composite flexible packaging materials with good barrier property. Despite of its excellent gas barrier, PVDC is hard to process and costs too much in production.
1.2 PET
PET is short for polyethylene terephthalate and the most commonly used PET currently is linear PET. Linear PET has the highest strength among all thermoforming materials and it features excellent thermal stability and wear resistance, melting point between 255 – 260 °C, higher rigidity than a lot of engineering plastics, low water absorption, small coefficient of linear expansion and high dimensional stability. Although its permeability is lightly higher than that of PVDC, it is still one of drug blister packaging materials with good gas barrier. For PET membrane with thickness of 0.25 mm, oxygen permeability is 2.9 cm per h MPa barometric pressure. Moreover, its moisture absorption is low: when soaked in water at 25 °C for a week, its water absorption is less than 0.6% and it maintains good dimensional stability.
J. R. Whinfield in UK developed PET with high melting point and good crystallinity for the first time based on research of W. H. CarOtherS in Du Pont CO. in U.S. and obtained relevant patent in 1946 with the product name of Terylene; in 1953, ICI CO perform trial production of PET membrane for the first time and named it Melinex; in 1954, Du Pont also produced membrane and named it Mylar; in 1959, Japan introduced ICI patent to produce PET and in 1963, it production reached 2,050 t. As a blister machine’s forming material, PET is superior to PVC in mechanical strength, transparency, resistance to bacteria & coldness, water absorption and toxicity, therefore, it is safer and more convenient for storing drugs in damp environment and has better barrier property than PVC.
1.3 COC
Overthrowing the traditional view of inadequate transparency of polyolefin crystals, COC combines strengths of crystalline and noncrystalline polymers, such as high transparency, high thermal resistance, low water absorption & permeability and finds wide application in drugs and foods. High-molecular polymers containing cyclic olefin monomer have been discovered a few years ago. But due to inability to control production process, their production was limited at that time and few products appeared for commercial application. Now copolymerization percentage of flexible linear olefin and rigid cyclic olefin monomers can be adjusted freely, rendering COC combined advantages of crystalline and noncrystalline polymers. However, despite its excellent thermal forming performance, it is fragile and hence often compounded with PP to help maintain shape. Now COC can be formed on thermal forming equipment and its easiness to form makes it an ideal blister packaging material just as PVC. Additionally, COC contains chlorine or other halogens and has no environmental pollution, good dimensional stability and high transparency after blister packaging for it is a crystal transparent object.
1.4 ACLAR
ACLAR uses new homopolymer material and has good forming performance with no need to apply coating on forming mould surface of blister packaging machines. But if forming mould has small angle or is complicated in some part, moulds with surface coating can help the material to be evenly distributed within the entire mould cavity. ACLAR’s barrier property can meet wide range of packaging requirement; it does not melt or stick to moulds, but it has high friction coefficient which will complicate mould design. If blister machine’s forming moulds have complicate shape, it is recommended to install ejector pin in moulds. Moreover, heating plate for forming should have reticulate pattern on the surface and smooth anti-sticking coating to reduce dragging of materials.
1.5 PP
As public awareness of environmental protection raises, PP becomes increasingly popular in international drug packaging. Modified PP features excellent air tightness, transparency & insulation, high impact strength and good processing performance without toxicity or danger. It can be used widely in drugs and foods in place of PVC. PP has good transparency, stiffness and appearance effect as well as excellent gas and water barrier performance and can ensure long shelf life of drugs inside. As a blister packaging material for drugs, it has good processing performance, mature process, good production efficiency and recycling function, good for environmental protection. Since it can effective protect damage to pharmaceutical ingredients by gases, sunlight and other media, it can be used in regions with any kind of climate. Especially, it is ideal for protecting quality of high-grade and new drugs prone to decomposition and chemical changes. It can be applied to packages of pills, tablets, suppository, capsules and pastille and is easy to open.
Jornen Machinery
25-11-2019