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Water Activity USP <795> Changes

Fri, 09/06/2019
Water Activity USP <795> Changes

Beyond-use dating in the newly published USP <795> guidelines set to go into effect December 2019 have made big changes to the recommended maximum beyond-use dates for different types of formulations.


One of the biggest changes is a new focus on microbial growth and preservative efficacy. The guidelines specify aqueous preparations as those having a water activity (Aw) greater than 0.6, and only preparations with an Aw less than or equal to 0.6 are considered nonaqueous or solid dosage forms.1

What is Water Activity?

Water activity is a measurement of the ratio of vapor pressure of the substance in question when at equilibrium with the surrounding air to the vapor pressure of distilled water under identical conditions.2 For example, a water activity of 0.6 means that the vapor pressure of the substance in question is 60% of that of pure water. Water activity should not be mistaken for water content. Water content is a measure of how much water is in a particular substance by weight or volume, whereas water activity is a measure of water that is available for reaction or accessible to microbes. Even items with relatively low water content can still have relatively high Aw.

Why Does Water Activity Matter?

Water activity is a fairly reliable measure of a microbe’s ability to grow in a particular substance. Generally, bacteria can grow at Aw greater than 0.85, and fungi such as yeasts and molds at Aw greater than 0.6.3,4 Newly published USP <795> guidelines consider anything with an Aw equal to or less than 0.6 to be nonaqueous, and therefore can be given longer recommended maximum beyond-use dates without necessarily having a preservative.1 Water activity is also a useful reference parameter when considering how much water is available in a substance to act in chemical reactions, potentially resulting in degradation of active ingredients in that substance.5

What Does This Mean for My Practice?

This new focus on Aw not only means a change in beyond-use dating guidelines, but also a new focus on preservatives and how to select one for a particular compounded preparation. The frequently asked questions page on USP’s website clarifies that these new guidelines do not require compounders to measure Aw for particular compounds and that these markers are intended to be used as a guide.6 It refers to General Chapter 1112 (Application of Water Activity Determination to Nonsterile Pharmaceutical Products) which provides a list of approximated Aw for various products.6,7 If Aw is not tested for a water containing preparation such as a cream or suspension, the Aw should be assumed to be greater than 0.6 and, in the absence of an appropriate study, the beyond-use date should be consistent with the maximum beyond-use date listed in table 3 of new USP 795 guidelines.1 In the absence of explicit data on a particular compound, General Chapter 1112 provides a good resource for justifying an assigned beyond-use date.

Fagron Anhydrous Base Options (Aw <0.6)

TOPICAL PREPARATIONS

  VEHICLE BENEFITS
Anhydrous Ointment Base™
Anhydrous Ointment Base
  • Thick ointment base containing petrolatum and mineral oil
  • Occlusive and could be considered for application to dry skin due to emollient properties
  • Contains emulsifier to improve the ability to hold solvent
Hydrophilic Petrolatum
Topical base
  • Thick ointment base containing petrolatum
  • Occlusive and could be considered for application to dry skin due to emollient properties
  • Capable of incorporating aqueous solvents due to added emulsifiers

 

Jelene®
Topical base
  • Plasticized ointment base containing polyethylene and mineral oil
  • Can be applied topically or mucosally and is commonly used in dental gel preparations
  • Water repellant, so preparations applied mucosally are resistant to removal by saliva, allowing time
  • for drug delivery to a specific area
  • Compatible with a wide range of APIs

 

Nourisil™
Anhydrous Silicone Base
  • Anhydrous silicone base with a silky skin feel
  • Contains vitamin E and silicone to confer improved hydration
  • Frequently used topically for wound and scar type preparations or added in concentrations of ~10%
  • to other creams to improve feel and silkiness
  • Compatible with a variety of APIs

 

Occluvan™
Hydrophilic Ointment Base
  • Anhydrous hydrophilic ointment base with vitamin E and natural oils for hydration
  • Often used topically but safe for mucosal and rectal use as well
  • Compatible with a wide range of APIs and solvents

 

 

Click here for the full list of Anhydrous options