Conclusion
An equation for the calculation of MKRH is based upon the humidity-corrected Arrhenius equation, which has been shown to be
applicable to a wide variety of solid-state pharmaceutical products and active substances. The calculation of the MKRH requires
a moisture sensitivity parameter, B, to be known, analogously to the way Ea is required for the calculation of MKT. In many situations, such as those involving chemical degradation, the use of MKRH
is more appropriate than the use of the arithmetic mean relative humidity, in much the same way that MKT is more appropriate
than the use of arithmetic mean temperature.
It is relatively simple to calculate the MKRH for constant temperature situations or to calculate the MKT for constant humidity
conditions using established methods, such as those described in USP <1150> (4). In situations that have both variable temperatures and humidity conditions, it may be necessary to use a combined
temperature and relative humidity calculation as described above, which provides a continuum of constant temperature and constant
relative humidity combinations that would age the product to the same degree as the set of variable temperature and variable
relative humidity conditions. However, in most situations, this combined calculation is not likely to be necessary, because
either the relative humidity can be considered to be effectively constant (e.g., when considering packaged products over short
time periods, such as with temperature excursions that occur during the distribution of products), or the temperature can
be considered constant (e.g., during stability testing of packaged products in which the relative humidity inside the packaging
changes dynamically over time and testing occurs at specific conditions, such as 25 °C/60% RH or 40 °C/75% RH). Despite its
limitations and its apparent complexity, the MKRH approach should prove useful in a number of pharmaceutically relevant situations,
as has the analogous concept of MKT.
Acknowledgments
The author would like to thank Ken Waterman for his inspirational scientific guidance and Bill Porter for stimulating technical
discussions. The author would also like to thank Tim Lukas, Bruno Hancock, and Pierre Barratt for their useful comments and
feedback.
Garry Scrivens, PhD, is in Pharmaceutical Sciences at Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, UK, CT13 9NJ, tel.
+ 44 0 1304 649578, garry.scrivens@pfizer.com
.
Submitted: Mar. 2, 2012; Accepted Mar. 28, 2012.
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