Mean Kinetic Relative Humidity: A New Concept for Assessing the Impact of Variable Relative Humidity on Pharmaceuticals

This article introduces the concept of "mean kinetic relative humidity" (MKRH) for evaluating the impact of humidity variability on the stability of solid-state pharmaceuticals analogously to the way mean kinetic temperature (MKT) is used for assessing the impact of temperature variability.
Nov 02, 2012
Volume 36, Issue 11

It is well established that the rate of chemical degradation of solid-state pharmaceutical products, such as tablets and capsules, is highly dependent upon the environmental temperature and humidity. Indeed, this concept is the underpinning theoretical basis for the pharmaceutical industry guidelines that provide recommendations for long-term, intermediate, and accelerated storage conditions and for establishing expiration dates (1).

The concept of mean kinetic temperature (MKT) was first introduced in 1971 (2) and was further developed in the 1990s (3). MKT can be defined as the single calculated temperature at which the total amount of degradation over a particular period is equal to the sum of the individual degradations that would occur at various temperatures (4). Thus, MKT may be considered as an isothermal storage temperature that simulates the effects of variable storage temperature. The MKT has been found to be useful in a number of pharmaceutically relevant applications, such as providing a scientific means of summarizing variable climatic temperatures (5), handling storage and distribution of pharmaceuticals (6), and for handling temperature excursions (7). The MKT is distinct from the simple arithmetic mean temperature and is generally accepted as a more scientific basis for summarizing variable temperature than the arithmetic mean temperature.

For assessing the impact of variable humidity conditions, on the other hand, no analogous concept to MKT has yet been proposed, because there has been no established means of relating the rate of degradation with humidity. The simple arithmetic mean, therefore, is most commonly used currently for most pharmaceutical applications. As far back as 1977, however, a mathematical relationship between the relative humidity (RH) and the reaction rate in the solid state has been suggested (8), and work by Waterman et al. has since demonstrated that this relationship is widely applicable to pharmaceutical products (9–12). This relationship allows a mean kinetic relative humidity (MKRH) to be calculated analogously to MKT. This article proposes a method for calculating MKRH, and the author discusses the advantages of using MKRH over the simple arithmetic-mean relative humidity and the limitations of the MKRH approach.