Water Activity

Scientist Live: “Pharmaceutical Industry Trends”

June 22, 2021 – Scientist Live
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 utilization 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 program.  

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. Practivally, it is measured as the partial vapor pressure of water in a headspace that is at equilibrium with the sample, divided by the saturated vapor 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 the 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 strength 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
  • Optimizing 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 optimizing  product stability. With a product’s water activity at is ideal range, pharmaceutical products will avoid stability breakdown and qualify for reduced microbial limits testing, resulting in time savings and reducing production costs.

Water Activity Test Time: It’s the Sample, Not the Instrument

There can be an abundance of confusion with water activity instruments concerning test time. Some instruments claim a 5-minute test time while others offer fast or quick modes. The truth is that water activity test time is determined by the sample and not the instrument. Since water activity is an equilibrium measurement, a reading is not complete until vapor equilibrium has been achieved and this process cannot be sped up by an instrument (1). So, any claim to a specific test time is illogical and would only be true for select samples. The reality is that most types of samples require a minimum of 5 minutes or more to reach true equilibrium and test times that are faster than that are either using a prediction or the system uses end-of-test settings that are not stringent enough to achieve true vapor equilibrium.

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shelf-life products
Scientist Live: “Accuracy Needed In Shelf-life Modelling”

January 4, 2022 – Scientist Live
Dr. Brady Carter on modelling shelf life with water activity
The shelf life of a product is defined as the practical time that it remains desirable to consumers. It dictates the radius of distribution for the product, how it must be stored and its best by date. Failure to match this expected shelf life can result in customer complaints, product recalls and tarnished reputation. Consequently, correctly determining the optimal production process and handling that maximizes the shelf life and then monitoring to make sure those conditions are met is the difference between profitability and lost revenue.

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water in a flask in the laboratory
Water Activity Standard Methods and Testing Regulations

Water activity testing, gauged by using a water activity meter, is most often used to determine the shelf life of a food product. It is important to gauge the amount of water in a food as it is known that water activity above 0.95 a w will provide sufficient moisture to support the growth of bacteria, yeast, and mold. Because it predicts stability relative to microbial growth, their rates of deteriorative reaction, and physical properties, water activity is considered to be an important property in the field of microbiology. In fact, regulatory agencies such as the Association of Official Analytical Chemists (AOAC), International Organization for Standardization (ISO), American Society for Testing and Materials, (ASTM) United States Pharmacopeia (USP) and a host of American, Canadian and International governments, have incorporated water activity standards into their safety regulations. If the water activity of food is controlled to 0.85 a w or less in a finished product, it is considered regulation-compliant.

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