USP Method <1112>

Microbiological Attributes of Non-sterile Pharmaceutical Products Application of Water Activity Determination

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Exact Reference

USP 29-NF 24* - Published April 2006
<1112> Application of Water Activity Determination to Non-sterile Pharmaceutical Products

*The United States Pharmacopeia- National Formulary (USP-NF) is a book of public pharmacopeial standards. It contains standards for medicines, dosage forms, drug substances, excipients, medical devices, and dietary supplements. The U.S. Federal Food, Drug, and Cosmetics Act designates the USP-NF as the official compendia for drugs marketed in the United States.

History

• Stimuli to the Revision Process article: Friedel, R.R. and A.M. Cundell. The application of water activity measurement to the microbiological attributes testing of non-sterile over-the-counter drug products.
  Pharmacopeial Forum 24(2):6087-6090 [Mar.-Apr. 1998].
• Stimuli to the Revision Process article: Friedel, R.R. The application of water activity measurement to microbiological attributes testing of raw materials used in the manufacture of non-sterile pharmaceutical products.
  Pharmacopeial Forum 25(5):8974-8981 [Sep.-Oct. 1999].
• Published as a draft chapter in
  Pharmacopeial Forum 28(6) 2009-2013 [Nov.-Dec. 2002].
• It appeared again revised as an In-process Revision in
  Pharmacopeial Forum 30(5): 1709-1712 [Sept.-Oct. 2004].
• Microbiology and Sterility Assurance (MSA) Expert Committee approved it for official status in April, 2006.

Synopsis

Reduced water activity will greatly assist in the prevention of microbial contamination of pharmaceutical products, and the formulation, manufacturing, and testing of non-sterile dosage forms should reflect this parameter.

Water activity has been extensively used in the food industry to prepare products with a low risk of microbial contamination. Extended to the cosmetic industry and could be successfully employed in the consumer health and pharmaceutical industries.

The determination of the water activity of non-sterile pharmaceutical dosage forms aids in the decisions relating to 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>.

How Dewpoint is Used to Measure Water Activity

The USP recommends using the Official AOAC International dew point/chilled mirror method to measure water activity.

Dew point is a proven primary measurement of vapor pressure. Dew point instruments are accurate, fast, simple to use, and precise. The water activity measurement range of commercially available dew point meters is 0.030 to 1.000, with a resolution of ±0.001 and accuracy of ±0.003. Measurement time is typically less than 5 minutes.

The basic principle involved in dew point determination of vapor pressure in air is that air may be cooled without changes in water content until the air saturates. The dew point temperature is a temperature at which the air reached saturation. It is determined by measuring the temperature of a chilled mirror when condensation begins. The water activity of the sample is the ratio of the saturation vapor pressure at the dew point temperature to the saturation vapor pressure at the product temperature.

In a dew point instrument (AquaLab), the sample is equilibrated within the headspace of a sealed chamber containing a mirror, optical sensor, internal fan, and infrared temperature sensor. At equilibrium, the relative humidity of the air in the chamber is the same as the water activity of the sample. A thermoelectric cooler precisely controls the mirror temperature. An optical reflectance sensor detects the exact point at the which condensation first appears. A beam of infrared light is directed onto the mirror and reflected back to the photo detector that detects the change in reflectance when condensation occurs on the mirror. A thermocouple attached to the mirror accurately measures a dewpoint temperature. The internal fan circulates the air, which reduces vapor equilibrium time and controls the boundary layer conductance of the mirror surface. Additionally, an infrared thermometer measures the sample-surface temperature. Both the dew point and sample temperatures are used to determine water activity. When measuring water activity, the dew-point temperature is repeatedly determined until vapor equilibrium is reached. Because the measurement is based on temperature determination, calibration is unnecessary, but a standard salt solution can be run to check the proper functioning of the instrument. If there is a problem, the mirror is easily accessible and can be cleaned in a few minutes.

Water Activity Measurement Solutions.

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