Water Activity: A Better Approach For Lyo Moisture Determination

By Derek Duncan, PhD, Lighthouse Instruments

Residual moisture content is a vital quality parameter for freeze-dried pharmaceutical products, which exist in various forms. Among these forms, only the relatively "free" water, as opposed to the more "bound" water, can trigger degradation events within the product. Despite this, the global pharmaceutical industry has historically standardized measuring total water content as the primary moisture quality parameter. Traditional moisture analysis techniques, such as gravimetric methods or Karl Fischer (KF) titration, are unable to differentiate between the different states of water. In contrast, many other industries, like the food industry, have adopted water activity measurement as their primary moisture quality parameter. Scientific research has demonstrated that water activity is a far superior predictor of product safety and stability compared to Karl Fischer's water content.

This article advocates for the pharmaceutical industry to shift from the traditional paradigm of total moisture content measurement to water activity. It presents concrete industry case studies demonstrating how non-destructive laser-based headspace water activity methods can be utilized to analyze the moisture content of freeze-dried pharmaceutical products. These methods facilitate the straightforward generation of statistical moisture data, which is crucial for optimizing lyophilization cycles, mapping moisture within lyophilization chambers, and characterizing batch moisture levels.

Discover how adopting water activity measurement can enhance product safety and stability to ensure higher quality and efficacy for consumers.