HPE Drug stability: What do we need to know? | Page 26

DATA EVALUATION
Evaluating stability data:
a summary
Stability studies reported in the literature continue to become more complex and there is a critical
requirement to ensure that infusions stored or used over extended periods remain effective and safe
Graham Sewell PhD
MRPharmS BPharm
MRSC CChem MBS CBiol
Professor of Pharmacy
Practice, De Montfort
University, Leicester, UK
The assignment of extended shelf-life or expiry
dates to aseptically prepared infusions or
injections is a common requirement in hospital
pharmacy practice. There are many reasons for
shelf-life extensions including:
• Small-scale aseptic batch preparation of infusions
to provide ready-to-use (RTU) injections or infusions
that are immediately available for use by clinical
staff without the need for further manipulation
• Small-scale batch preparation of high-cost
medicines to avoid wastage associated with part-
used vials when preparing individual doses
• Preparation of RTU standard doses of infusions or
injections for standardised treatment protocols or
for dose-banding schemes
• Reduction in waste when infusions are cancelled
after preparation or in cases where the dose
may be delayed, for example, abnormal blood
counts or renal function prior to a cycle of cancer
chemotherapy
• Where extended infusion storage and/or
infusion time are required, for example. the
ambulatory administration of antibiotic therapy or
chemotherapy using portable infusion pumps.
Infusions and injections for parenteral use are
normally aseptically prepared by diluting a sterile
concentrate supplied by the manufacture with a
sterile pharmaceutical diluent such as 0.9% sodium
chloride or 5% dextrose in a flexible infusion bag
or a syringe. In some cases, the concentrate may be
drawn up into syringes without dilution to provide
pre-filled syringes for RTU injection. Some drugs
are provided as sterile freeze-dried powders by
manufacturers, which require reconstitution prior
to dilution.
Types of stability
The above manipulations introduce significant
changes to the chemical and physical environment
of the drug which can influence the stability of
both the drug and the overall infusion or injection.
Infusion stability comprises three components;
chemical, physical and microbiological stability.
Chemical
Chemical stability relates to any changes in
the chemical structure of the drug molecule
resulting from chemical degradation. In the case
of macromolecules or biologics, such as mAbs, the
degradation may involve conformational changes to
secondary and tertiary molecular structures, altering
the three-dimensional characteristics of the drug
molecule.
Chemical degradation in infusions/injections
can occur because of unfavourable pH changes
following dilution, leading to acid- or base-catalysed
hydrolysis reactions, from the presence of strong
nucleophiles, such as chloride, in the diluent which
promote nucleophilic substitution reactions, or
from dissolved oxygen in the infusion resulting in
oxidation reactions. Some drugs are light-sensitive
and can be degraded if certain wavelengths of light
are not filtered by the container or light-protective
overwraps. Other factors such as temperature
and drug concentration can also affect the rate of
chemical degradation.
Chemical stability is critical because degradation
might significantly reduce drug efficacy. In most
cases the exact identity of all degradation products
has not been fully determined, and little is known
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