HPE Drug stability: What do we need to know? | Page 5

Stability testing of the drug product in the final
package material will provide information on the
recommended storage conditions (for example,
room temperature or refrigerated) and the shelf-life
of the drug product.
Expiration date (or expiry date)
This is the date until which the manufacturer
guarantees full potency and safety of the product.
It can be a fixed date after manufacturing (for
example, for solid dosage forms), date after
reconstitution of solutions or aqueous suspensions
from solid powder (for example, for parenteral
solutions and oral antibiotic mixtures), or the date
after opening the drug container (for example, for
eye drops).
Factors affecting drug stability
A number of factors affect drug stability, ranging
from weighing of active ingredients and excipients
of formulations through to packaging, storage and
handling conditions (see Table 2). 3
High temperatures accelerate oxidation and
hydrolysis reactions, which cause drug degradation.
Similarly, acidic and basic pHs can impact on
degradation of most drugs. Many drugs are stable
within the pH range 4 to 8. Moisture in the
formulation also endorses microbial growth and also
catalyses hydrolysis and oxidation reactions. Liquid
TABLE 2
Factors
affecting
stability
• Temperature/
humidity
• pH
• Moisture/presence
of liquid
• Exposure to oxygen
• Adsorbtion/reaction
with surfaces of
containers
• Light (certain
wavelengths of light)
• Initial handling
and preparation/
compounding accuracy
drug formulations can be less stable than solid
dosage forms due to presence of water. Exposure
of a drug to oxygen can cause oxidation reactions
that can affect the stability. Besides these, packaging
materials, especially of the container and closures,
are important in drug stability. Adsorption of drug
or other components onto surfaces of containers
can potentially reduce the therapeutic effect,
especially at low drug concentrations. Moreover,
storage conditions for the drug formulations are
also significant because changes in temperature
and humidity can influence stability. Some drugs
are light-sensitive and can be degraded by certain
wavelengths of light if not adequately protected.
Degradation pathways
The most common chemical degradation mechanisms
are hydrolysis and oxidation. Other common
degradation mechanisms are isomerisation,
photochemical degradation, decarboxylation,
dehydration and polymerisation (see Table 3).
In general, drug degradation is both pH- and
temperature-dependent. In addition, common
water impurities, such as metal ions, and light can
catalyse drug degradation. The rate of reaction, such
as drug degradation, can be defined as the rate of
concentration changes of the reactant (that is, the drug
or API). The average kinetic energy of the reacting
molecules increases with increasing temperature,
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