Water Activity: A Faster Alternative to Traditional Testing of Non-Sterile Products in the Pharmaceutical Industry

 

Water Activity: A Faster Alternative to Traditional Testing of Non-Sterile Products in the Pharmaceutical Industry

The microbial limit test (also known as the traditional testing method) is a time-consuming test adopted by most of the pharmaceutical industry for the release of non-sterile commercial products to market after completing their manufacturing processes. The test is generally done as per USP <61> (Microbial Enumeration Tests) for total aerobic microbial count (TAMC) and total yeast/mold count (TYMC). USP <62> (Tests for Specified Microorganisms) for the presence or absence of specific objectionable pathogens. Total time consumed to complete the test is between 5 and 7 days. The cost of the test is high because of consumption time, manpower, culture media, and the utilization of different equipment for a single test.

Water activity (aw) is the ratio of vapor pressure of H₂O in product (P) to vapor pressure of pure H₂O (Po) at the same temperature. It is numerically equal to 1/100 of the relative humidity (RH). Water activity (aw) is an important parameter for the growth of microorganisms. Practically, the water activity test can be performed and completed between 1- 2 hours. So we can say the test is less time-consuming and also a cost-effective test in comparison to the microbial limit test. Also single equipment is used for the test.

Rationale for selection of water activity (aw) as an alternate method

Most of the bacteria isolated from compressed tablets grow above water activity (aw 0.75), and yeast and molds above (aw 0.60). (Ref. USP. 35, (1112) “Application to water activity determination of non-sterile pharmaceutical products”) Estimated water activity (aw) of compressed tablets is between 0.30 and 0.40, which is very low for vegetative microorganisms to grow and multiply, but the spore-forming organism, if present in compressed tablets, can remain in a dormant phase, which can grow as a colony during the microbial limit test due to getting a favorable environment.

Assessment study of compressed tablets for water activity test and comparison with microbial limit test.

Microbial tests were done as per USP <61> (Microbial Enumeration Tests) and USP <62> (Tests for Specified Microorganisms). A water activity test of compressed tablets was done by crushing the compressed tablets in a clean, dry mortar and pestle, and the test was done using a water activity meter (Novasina). Before conducting the water activity test, the equipment was calibrated using SAL-T 58, SAL-T 11, and SAL-T 84  standard provided by the manufacturer.

Result

S.No	Products	Observed Value (Initial test)		Observed Value (12 month Real time stability)
		Water activity (aw)	Microbial Limit Test	Water activity (aw)	Microbial Limit Test
1	Chlorthalidone 6.25 mg tablet	0.430@25.8°C	10 Cfu/g	0.433@25.1°C	10 Cfu/g
2	Chlorthalidone 12.5 mg tablet	0.315@25.4°C	0 Cfu/g	0.327@24.9°C	10 Cfu/g
3	Chlorthalidone 25 mg tablet	0.346@25.9°C	20 Cfu/g	0.356@25.0°C	20 Cfu/g
4	Amlodipine 5 mg tablet	0.511@25.6°C	30 Cfu/g	0.510@25.2°C	20 Cfu/g
5	Methylcobalamin 1500 mcg tablet	0.432@25.2°C	10 Cfu/g	0.427@25.1°C	10 Cfu/g

Result Interpretation 

Small sample size studies were done under laboratory conditions for comparison between the microbial limit test and water activity (aw) to find the relation of water activity for microbial growth. The result was found in agreement with USP 35, (1112) “Application to water activity determination of non-sterile pharmaceutical products,” as the growth of organisms did not significantly increase in the test result. The water activity was found below 0.75 in all samples, and the load of organisms during the initial test and 12-month real-time stability did not vary drastically.

Conclusion 

Based on our test result, we can conclude that the water activity test can be used as an alternate method for testing compressed tablets in the pharmaceutical industry for immediate batch release, changing the testing method to an automated method and saving time and cost to increase productivity and cost-effectiveness within the pharmaceutical industry. 

Limitation of study 

1. The sample size of the study is too small to draw any realistic conclusion.

 Recommendation

 Any manufacturing industry that wants to implement water activity as an alternate method  to the microbial limit test ,is suggested to test the large sample size under their own laboratory condition before implementation of alternate method.