Water Activity and its Importance to Drug Product Quality

What is water activity?

In compounded preparations, water activity refers to the water in a drug product freely available to participate in reactions such as hydrolysis or provide an environment that supports microbiological growth. Measuring water activity is important because many drug products include water in their formulations and are sensitive to water exchanges with the environment. 

How much water activity is required to support microbial growth?

USP <1112> Table 1 lists water activity values required to support the growth of microorganism species. If water activity falls below that value, microbial growth is suppressed.


What is the connection between water activity values and the beyond use dates in the proposed 2021 USP <795>?

In the proposed 2021 USP <795>, USP details the role of water activity in determining BUD limits for preparations. The proposed chapter defines aqueous and nonaqueous dosage forms based on water activity:

  • Aqueous - water activity measurement ≥ 0.6
  • Nonaqueous - water activity measurement < 0.6

Why do drug products with water activity below 0.6 have a longer BUD limit?

Dosage forms with water activity < 0.6:

  • Prevent microbial proliferation
  • Improve the antimicrobial effectiveness of preservatives
  • Reduce the likelihood or amount of active pharmaceutical ingredient degradation due to hydrolysis 
  • Decrease the frequency of microbial limit testing and screening for objectionable organisms for product release and stability testing

How is the water activity value determined?

  • There are representative examples of different dosage forms and their water activity values in USP <1112> Table 2 and proposed 2021 USP <795> Table 3. 
  • Testing the drug product can also determine water activity values. Water activity is measured by calculating the vapor pressure of water in the test sample relative to the vapor pressure of pure water at the same temperature. ARL’s water activity instrument uses a chilled dew point sensor to measure water activity with ± 0.003 accuracy.

For more information on water activity, contact ARL at info@arlok.com or 800-393-1595.