Is Water Activity measuring a legit alternative to micro testing for Dietary Supplements and Pharmaceutical products?
Are you refering to a particular type of pharmaceutical ?--powdered raw materials typically have bioburden limit.
Thanks for responding. I am talking for finished tablets of Multivitamins and OTC drugs as well as raw materials used to meake them.
Typically there is a limit of somewhere near 800 cfu/gm--based on whats attainable in non-sterile manufacturing processes. For media manufacturing one way to keep the bioburden low is to maintain as low a water activity as possible during the processing steps and control of time and tempeatures during steps requiring greater levels of water.
Here are a couple of very good article dealing with using water activity for testing OTC Drug Products and their raw materials.
Friedel R.R. and A.M. Cundell. (1998) "The Application of Water Activity Measurement to the Microbiological Attributes Testing of Nonsterile Over-the-Counter Drug Products," Pharmacopeial Forum, Vol. 24, No. 2, pp. 6087-6090.
Friedel R.R. (1999) "The Application of Water Activity (aw) Measurement to the Microbiological Attributes Testing of Raw Materials Used in the Manufacture of Non-Sterile Pharmaceutical Products," Pharmacopeial Forum, Vol. 25, No. 5, pp. 8974-8981.
Below is the abstract and introduction to a recent article that was published in the PMF Newsletter, Vol 12 (10) 2006 concerning water activity testing for pharmaceutical products using USP <1112>.
The article contains some great tables for key water activity literature references, miminum water activity required for growth of common bacterial isolates, and typical water activity values for common pharmaceuticals and OTC drugs.
You can download a pdf of this newsletter at http://www.microbiologyforum.org/PMFNews/PMFNews.12.10.0610.pdf
Water is recognized as being very important, if not critical, to the chemical, physical, and microbiological stability of most pharmaceuticals. Controlling the water within a product, by chemically or structurally binding it or else through some method of drying has long been used in the pharmaceutical industry. Water activity is a measure of the energy status of water in a product and is reduced through chemical binding or drying. Its not the amount of water, but rather the water activity that plays a critical role in the microbiological,
chemical, and physical stability of pharmaceutical dosage formulations and ingredients. Knowledge of the water activity of pharmaceuticals is essential to obtain a dosage formulation with optimal shelf life properties. Introduction Water activity is defined as the ratio of the vapor pressure of water in a material (p) to the vapor pressure of pure water (po) at the same temperature. Relative humidity of air is defined as the ratio of the vapor pressure of air to its saturation vapor pressure. When vapor and temperature equilibrium are obtained, the water
activity of the sample is equal to the relative humidity
of air surrounding the sample in a sealed measurement
chamber. Multiplication of water activity by 100 gives the equilibrium relative humidity (ERH) in percent. aw = p/po = ERH (%) / 100 As described by the above equation, water activity is a ratio of vapor pressures and thus has no units. It
ranges from 0.0aw (bone dry) to 1.0aw (pure water). There are several factors (osmotic, matrix, and capillary) that control water activity in a system. It is a combination of these factors in a product that reduces the energy of the water and thus reduces the vapor pressure above the sample as compared to pure water. Water activity is a measure of how tightly water is
bound and related to the work required to remove water from the system. Due to varying degrees of osmotic and matrix interactions, water activity describes the continuum of energy states of the water in a system rather than a static boundness. Water that is bound should not be thought of as totally immobilized. Microbial and chemical processes are related to waters bound energy status in a fundamental way. Since moisture content only provides information about the amount of
water and not the availability or boundness of water, it is
unreliable for determining susceptibility to microbial
growth. Because water is present in varying energy states,
analytical methods that attempt to measure total moisture in
samples dont always agree or relate to safety and quality.
For example, a product may contain a relatively large percentage of moisture, but if the water is chemically bound
with the addition of humectants or solutes, such as salts,
sugars, or polyols, the water is biologically unusable for the
microbial growth processes. The water activity concept has
served microbiologists and food technologists for decades
and is the most commonly used criterion for food safety
and quality, however water activity has not been widely
adopted in the pharmaceutical industry. Some key papers
describing water activity, its measurement, and pharmaceutical
applications are listed in Table 1.
Now there is a published USP (United States Pharmacopeial)
Method <1112> that utilizes water activity. USP
Method <1112> Microbiological Attributes of Non-sterile
Pharmaceutical Products Application of Water Activity
Determination provides guidance on the influence of water activity as it pertains to the susceptibility of a product formulation to microbial contamination. Knowledge of the behavior of microorganisms in pharmaceutical products at different aw levels is essential to effectively utilize USP method <1112>. The chapter discusses the potential for improving product preservation by maintaining low water activity. The determination of the water activity of non-sterile pharmaceutical dosage forms aids in the following:
Optimizing product formulations to improve antimicrobial
effectiveness of preservative systems Reducing the degradation of active pharmaceutical ingredients within product formulations susceptible to chemical hydrolysis Reducing the susceptibility of formulations (especially liquids, ointments, lotions, and creams) to microbial contamination Providing a tool for the rationale for reducing the frequency of microbial limit testing and screening
for objectionable microorganisms for product release and stability testing using methods contained in the general test chapter Microbial Limit Tests <61>
Great information! Thank you very much.