Biomedical Engineering Reference
In-Depth Information
• Long-term thermal stabilizers that provide defense against heat
encountered in end-use applications (e.g., hindered phenols and hin-
dered amines)
• Light stabilizers that provide ultraviolet (UV) protection through
mechanisms such as radical trapping, UV absorption, or excited-
state quenching
One application in which an additive can improve or alter the performance
of a polymer is a filler or modifier that affects its mechanical properties.
Additives known as
plasticizers
can affect the stress-strain relationship of
a polymer. Polyvinylchloride (PVC) is used for home water pipes and is a
very rigid material. With the addition of plasticizers, however, it becomes
very flexible and can be used to make intravenous (IV) bags and inflatable
devices. Lubricants and processing aids are also used to reduce polymer
manufacturing cycle times (e.g., mold-release agents) or facilitate the move-
ment of plastic and elastomeric components that contact each other (e.g., rub-
ber stoppers used in syringes).
Additives are not always single entities. Some are manufactured from
naturally occurring raw materials such as tallow and vegetable oils that are
themselves composed of many different components and can vary from
batch to batch. Others are considered “products by process,” as they are
formed during processing by adding several starting materials to affect the
chemical reaction. The complexity of chemical reactions that take place in
the manufacturing of plastic makes the analysis of extractables and leach-
ables very complex and difficult. In testing extractables and leachables, those
lesser-known minor chemical species may be the ones that leach into a drug
product, but this is not predictable as it is to a greater degree a function of the
characteristics of the product.
Stabilizers incorporated into plastics and rubbers are constantly working to
provide much-needed protection to the polymer substrate. This is a dynamic
process that changes according to the external stress on the system. For exam-
ple, good stabilizers are efficient radical scavengers. Generally, a two-tiered
approach is used to protect polymers from the heat and shear they encounter
during processing: using primary antioxidants (e.g., hindered phenols such
as butylated hydroxy toluene (BHT) or Ciba's Irganox) for protection during
processing can provide long-term heat stability. Secondary antioxidants are
also added as process stabilizers, typically hydroperoxide decomposers that
protect polymers during extrusion and molding and protecting the primary
antioxidants against decomposition. All the by-products of these reactions
become available to leach from polymers into a drug product.
Elastomers are also used for special stabilization: acid scavengers are used
to neutralize traces of halogen anions formed during the aging of halogen-
containing rubbers (e.g., brominated or chlorinated isobutylene isoprene).
If not neutralized, anions cause premature aging and a decrease in the
