Water Activity Measurement in Pharma

AW monitoring is key to product stability, quality and shelf-life

Water activity (aw) is – or should be – an essential quality measurement during the formulation and manufacture of a wide range of both solid and aqueous, non-sterile pharmaceutical products. Understanding water activity is important to prevent unwanted chemical reactions and microbial growth and unexpected changes in physical characteristics such as flow, compaction, hardness and rates of dissolution.

The total water content, or moisture content, of a pharmaceutical product or ingredient includes both the free water and bound water within the product.

• Bound water is a constituent part of the product, which is molecularly bonded to product ingredients, such as API or excipients, and is thus not readily available for most biological or chemical reactions with other components.
• Free water is by definition only loosely bound within the product. It can therefore act as a medium, which promotes reactions that affect the quality and stability of the pharmaceutical product and its ability to comply with regulatory requirements.

Water activity therefore is a measurement of only the free water available within a pharmaceutical product or ingredient and reflects the energy level of the water.

To learn more about the theory of water activity take a look at this water activity theory blog post

Microbial growth

Microbial growth is perhaps the most common problem associated with high levels of water activity. It has long been recognized that the availability of free water determines the ability of a pharmaceutical product to support the growth of microorganisms; also, that there is a level of water activity below which microbial growth cannot occur. This is different for each microorganism, but the lower limit is typically around 0.6 – the measurement scale for water activity being from 0.0 (completely dry) to 1.0 (water).

Other common problems caused by high levels of water activity

Microbial growth is not the only problem to be caused by high levels of water activity. Other potential threats to product quality or stability include moisture migration, which can lead to gel capsules fracturing due to a difference in water activity between the gel and the drug within the capsule.

High water activity can also accelerate chemical reactions, such as oxidation, hydrolysis and decomposition, causing loss of drug potency. Additionally, it can cause physical changes including disintegration, swelling and caking of powdered pharmaceuticals and, most importantly, introduce the risk that products may fail to meet the appropriate regulatory standards.

For example, stability testing is a regulatory requirement for every drug release program. The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) sets out test conditions to determine the dryness of each pharmaceutical product, with mandatory measurements including temperature and moisture conditions. The methodology is defined in ICH Q6A, where there is a clear implication that measuring and understanding the effects of water activity should be an essential part of any drug release quality program.

Controlling water activity

The correct level of water activity required for each pharmaceutical product can be controlled in a number of ways. Water activity levels can be reduced through the use of desiccants and vacuum or freeze drying, by blending the product with a material with a lower level of water activity, adding chemicals that bind the free water, and by the use of suitable moisture barrier packaging. The choice of control technique will depend on the product formulation, type, the different manufacturing, storage and transportation processes.

Measuring water activity

The most common and effective instruments for measuring water activity are dedicated portable units such as our AwEasy, which is ideal for spot measurements at any stage of the production process, or laboratory water activity meters and probes, such as our, AwTherm and HygroLab units. These have been designed to provide quick and accurate measurements and are available with a range of accessories and analysis software.

Other online process options include capacitive humidity sensors, which provide a precise measurement of relative humidity, or dew point meters to measure the temperature at which condensation occurs. Both these instruments provide measurements from within production and storage processes from which water activity can subsequently be calculated.

Learn more about our range of products for measuring water activity