How to determine water activity in pharmaceutical excipients

Protect excipients from degradation and prevent microbial growth

Excipients are inactive pharmaceutical ingredients that are added to pharmaceutical formulations alongside the active pharmaceutical ingredient (API) to enhance the drug's overall performance, stability and appearance.

Excipients are therefore important components in most pharmaceutical products. They play a vital role in the formulation of stable dosage forms to assist the manufacturing process, protect the API, act as a bulking agent and enhance the bioavailability (solubility, dissolution or permeability), safety or patient acceptance of the primary drug.

Many excipients such as pregelatinized starch, cellulose derivatives, magaldrate and gelatin are, in varying degrees, hygroscopic; in other words they will readily absorb moisture from the environment. This can lead to a number of potential problems that include:

• Degradation and spoilage of both the excipient and the API
• Changes in the chemical and physical properties of the product
• The growth of microorganisms and potential product contamination
• A reduction in the potency or efficacy of the active ingredient

Typically, excipients have a crystalline or am orphous matrix structure. Crystalline structures, in particular, can be susceptible to changes in moisture levels, measured as water activity (aw). For example, deviations in either waters of hydration or deliquescence – the absorption or loss of moisture – can affect the dissolution properties of pharmaceutical tablets and powders and degrade the efficacy of the API. In many instances, changes in water activity caused by poor temperature control of the surrounding environment can lead to sudden changes in material properties; this is especially true for deliquescence, where gradual increases in water activity have minimal effect, until a critical point is reached where a small additional increase causes a disproportionate rise in moisture content created a saturated state that has a dramatic effect on material properties.

By comparison, amorphous matrix structures normally exist in a low moisture, relatively stable glassy state. Nonetheless, these products can be susceptible to changes in temperature and water activity, where an increase in moisture content causes glass transition to take place, with the amorphous matrix gradually moving from a glassy to a rubbery state. Again, this can occur suddenly and have a significant impact on material properties such as structural collapse, reduction is dissolution properties and an increased propensity for caking or crystallization.

It is important to note that in both forms of excipient an increase in water activity above a critical point can create the conditions where microorganisms can begin to propagate.

The importance of measuring water activity

As will have been clear from the description above, the ability to measure water activity is essential for understanding and predicting the behavior of excipients under different conditions, as well as for quality control, traceability and regulatory compliance.

Once a particular excipient or drug product has been tested under different development, manufacturing and storage conditions it becomes possible to create a water activity profile, against which subsequent quality control monitoring can be benchmarked. In general terms, the key is to understand the critical water activity point at which changes in material properties may occur and then to ensure that process or environmental conditions are maintained such that water activity, and thus moisture content, cannot increase – or in some instances, fall – above or below this level.

As an example, excipients used as binders that allow powders to cohere in tablet formation will have unique water activity profiles, with an ideal aw value that corresponds to the desired optimal material characteristics when compacted into tablet form. Measuring the aw of the excipient before it enters the tablet process will indicate if it is outside tolerance and therefore likely to affect the hardness or solubility of tablets.

Measuring water activity can easily be carried out in the laboratory or on-site using hand-held probes and bench-top meters. The latest instruments are extremely accurate, simple to use, produce results quickly and are supported by advanced analysis and reporting software.

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We are the world’s leading experts in water activity, moisture monitoring and Dew Point measurement. We have eight different technologies covering all moisture applications, backed by unrivalled technical and customer support. To learn more, talk to one of our application specialists today.