Plastic packaging materials extractables

Although glass containers are very suitable for Hb packaging, flexible plastic containers constructed from materials such as poly(ethylene-vinyl acetate) (EVA) are most widely used. The plastic packaging material must be carefully selected. Hemoglobin, like other proteins, is lipophilic and can facilitate extraction of low molecular weight lipophilic substances, such as the plasticizers used in poly(vinyl chloride) containers. 

Various workers [68-72] have carried out extensive studies of the determination of total migration of additives from plastics packaging materials into edible fats using a C-labelled fat simulent (HB 307). Methods based on measurement of total extract into volatile solvents such as n-heptone and diethylether were rejected at an early stage [73-86]. 

Contaminants in recycled plastic packaging waste (HDPE, PP) were identified by MAE followed by GC-MS analysis [290]. Fragrance and flavour constituents from first usage were detected. Recycled material also contained aliphatic hydrocarbons, branched alkanes and alkenes, which are also found in virgin resins at similar concentration levels. Moreover, aromatic hydrocarbons, probably derived from additives, were found. Postconsumer PET was also analysed by Soxhlet extraction and GC-MS most of the extracted compounds (30) were thermally degraded products of additives and polymers, whereas only a few derived from the original contents... 

Some potential extractable chemicals from packaging materials are water soluble, while others are soluble only in nonpolar environments. The USP includes physicochemical tests for plastics based on water extracts, while water, alcohol, and hexane extracts are required for polyethylene containers under controlled temperature and time parameters (70°C for 24h for water and alcohol and 50°C for 24h for hexane). 

The USP general chapters do not specifically address safety for polyethylene (HDPE or LDPE), PP, or laminate components. A patient s exposure to substances extracted from a plastic packaging component (e.g., FIDPE, LDPE, PP, laminated components) into a liquid-based oral dosage form is expected to be comparable to a patient s exposure to the same substances through the use of the same material when used to package food [27]. 

Physicochemical testing is performed to characterize the physical and chemical properties of a plastic to insure that the composition of the synthetic medium will not compromise the quality of the drug being stored within it. To perform these tests, samples of plastic identical to the material being used in the primary package are subjected to an extraction procedure—to dissolve in an extraction solution leachable compounds that are at risk of entering the pharmaceutical preparation. This extraction solution is then subjected to analysis to evaluate the identity and quantity of leachants. For most plastics, the appropriate extraction medium is purified water, but elastomeric closures for use with injections should include extraction with three different extraction... 

Liquid oral preparations are usually contained in PET or PETG containers. PETG has a different polymeric composition than PET as discussed under Types of Packaging Materials. Physical characteristics are listed in the USP and 21 C.F.R. specifies their composition. Identification of PET and PETG shows that these plastics are distinct and distinguishable from one another by IR spectrum, but the two compounds are similar as evaluated by thermal analysis.f " This type of plastic should be tested for colorant extraction as previously discussed. " ... 

The first statement is the one that is to be followed, however, if this approach is accepted, glass should be excluded as a packaging material since it contains lead, though this lead cannot be extracted. Anyway, a new legislation is on its way. For many years the effective international control of additives has been done by the US FDA, and most plastics and additives are tested according to these standards. 

LCA includes the following important steps materials extraction, manufacturing and waste production, packaging, transportation, product use and product disposal. In order to calculate the amount of emissions and waste created during the life cycle of a product, much fundamental information is needed on manufacturing processes, materials and energy use. A life cycle inventory (LCI) is therefore compiled to record the emissions and resources consumed that can be attributed to a specific product. Databases have been developed that enable the user to input new information or data specific to their products and processes. Ecoinvent v3 (http //www.ecoinvent. org/database/) is probably the most comprehensive international LCI database. The ecoinvent database is included in most LCA software models. The following are some of the software suitable for LCA of plastics (O Neill, 2003) ... 

One of the important requirements of any packaging material is that it should not release any component into the drug product. Preparation of containers free of any leachables such as monomeric component is especially important for the containers of ophthalmics, parenteral products, and any liquid products. It was shown that di(2-ethylhexyl) phthalate was released from the PVC bags and that caused haziness of the taxol solution (37), USP/NF offers the protocol of chemical, spectral, and water vapor permeation tests and tolerances for plastic containers (55). Among those, chemical test is designed to give a quantitative assessment of the extractable materials in both organic solvents and water. 

Where direct contact occurs between the packed commodity and the plastic it is likely that some transfer of polymer additives will occur, adventitious impurities such as monomers, catalyst remnants, and residual polymerisation solvents, and low molecular weight (MW) polymer fractions from the plastic into the packaged material with the consequent risk of a toxic hazard to the consumer. The actual hazard arising to the consumer from any extractable present is a function of two properties, namely the intrinsic toxicity of the neat extracted material as evaluated in animal feeding trials (not dealt with in this book) and the amount of the extracted material from the polymer that enters the packed food under service conditions, i.e., during the packaging operation and during the shelf life of the food to the time of consumption. 

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