The control of moisture in pharmaceutical products is often necessary to prevent deleterious chemical and physical changes
to a product. Moisture-driven changes in solid oral dosage forms can have severe adverse effects on pharmaceutical quality.
Hence, several measurement approaches for product-moisture content currently are in routine use in the industry. Among the
most common means to ascertain moisture levels in solid oral dosage forms are destructive loss-on-drying (LOD) or Karl Fischer
(KF) titration techniques. An attractive augmentative approach for examining product moisture would be to directly determine
the chemical potential of water in the sample by means of water activity (A
), which is an arguably more fundamental indicator of the available water for the promotion of chemical, physical, or biochemical
change (1–4). The chemical potential of a component in a mixture—such as water—is a fundamental measure of the "escaping tendency"
or the availability of the component in the mixture, rather than the total moisture (which may include water that is bound
or otherwise unavailable).
At typical storage temperatures and humidities for pharmaceutical solids (5–40 °C and <85% relative humidity), water behaves
like an ideal gas, and the activity of water in a solid can be related to the headspace relative humidity by the following
~ (PW ÷ PWS ) = (relative humidity ÷ 100)
in which PW is the partial pressure of water in the headspace, and PWS is the saturated vapor pressure of water at the temperature of interest.
Thus, the relative humidity in the package headspace over a pharmaceutical solid at equilibrium can be directly related to
the water activity and is an indication of the amount of water present with potential to cause undesirable changes in the
Currently, two different types of water activity instruments are commercially available: one based on a chilled-mirror dew-point
technology to measure humidity and the other based on a polymeric thin-film capacitance sensor that is responsive to headspace
moisture. In both of these techniques, the sample of interest is equilibrated in a sealed chamber until equilibrium between
the solid and headspace moisture is reached. The chilled-mirror instrument consists of an optical reflectance sensor that
detects the exact point at which condensation first appears at the mirror–headspace gas interface. This point is determined
by directing a beam of infrared light onto the mirror surface and reflecting the beam of light to a photodetector, which detects
reflectance changes upon initiation of condensation. A thermoelectric (Peltier) cooler helps to control the mirror temperature
precisely, and a thermocouple attached to the mirror accurately measures the dew-point temperature. Both the dew-point and
measured sample-surface temperatures are then used to determine the water activity.