Pharmaceutical Industry Trends

Dr Brady Carter discusses the new standard for water activity measurement

Water activity has been broadly used in the pharmaceutical industry since the publication in 2006 of USP <1112>, an informational chapter on the application of water activity in pharma. Although <1112> provided guidance for the utilisation of water activity, it was not an official method. Now USP has developed USP <922> Water Activity as an official method that will hopefully further facilitate its implementation as an integral part of a pharmaceutical quality programme.

What is Water Activity?

Water activity is defined as the energy status of water in a system and is rooted in the fundamental laws of thermodynamics. Practically, it is measured as the partial vapour pressure of water in a headspace that is at equilibrium with the sample, divided by the saturated vapour pressure of water at the same temperature. Water activity is often incorrectly referred to as “free water,” which is misleading because “free” is not scientifically defined and is interpreted differently depending on the context.

Recommendations for the determination of water activity are outlined in USP <922> Water Activity. This method became official in May 2021 and provides guidance for water activity measurement. It includes a brief theoretical background explanation and discusses some factors that influence water activity including solute concentration and temperature. It also provides a short review of the various sensor types available for measuring water activity and highlights the strengths of each. It provides guidance on the qualification of instruments and highlights that water activity meters should be calibrated using standard solutions and this should be done at a minimum yearly or whenever a calibration check fails. Calibration verification checks should be conducted daily based on the instructions from the instrument manufacturer and using a minimum of two standards that book-end the typical water activity range.

In terms of suggested uses for water activity, USP <922> extends beyond the usage suggestions of USP <1112> to include:

  • Selecting ingredient isolation and product manufacturing process conditions in terms of maintaining aw below the critical threshold to obtain thermodynamic control of the desired solid form (e.g., hydrate versus anhydrate)
  • Selecting excipients for which aw may impact their material flow, compression characteristics, hardness, and performance characteristics(e.g., disintegration and dissolution) of dosage forms
  • Reducing the degradation of active ingredients within product formulations
  • Establishing the level of protection to product formulations to moisture by primary packaging materials during their shelf life
  • Controlling and monitoring physical, chemical, and microbial product stability
  • Optimising formulations to improve the antimicrobial effectiveness of preservative systems
  • Providing a tool to justify the reduction of microbial testing of nonsterile drug and dietary supplements formulations

Water activity is sometimes an overlooked and underestimated parameter in pharma quality and formulation. However, USP <922> highlights how it offers critical information for optimising product stability. With a product’s water activity at its ideal range, pharmaceutical products will avoid stability breakdown and qualify for reduced microbial limits testing, resulting in time savings and reducing production costs.

Dr Brady Carter is an application scientist with Novasina

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