How to Test Particulate Matter

Fluids and drugs meant for direct injection into the blood stream need to be free from particulate matter. If dust particles, formulation ingredients, environmental contaminants and packaging ingredients find their way into these products, it poses a danger to the patient receiving them. Particulate matter has the potential to cause vein irritation, occlusion of arteries and capillaries, pulmonary dysfunction, anaphylactic shock and even death. The United States Pharmacopoeia prescribes two tests for particulate matter in intravenous use preparations.

Instructions

• 1

  Determine which of the two testing procedures to use, depending on the nature of the preparation to be tested. The light obscuration particle count test is the preferred method. However, this method is not applicable if the preparation is one with high viscosity or low clarity such as an emulsion or a liposome-containing preparation. In such cases, use the microscopic particle count test.

• 2

  Draw samples from the batch of products. Use a sampling plan that is statistically strong to ensure you obtain samples that are representative of the entire batch. This increases the validity of your inferences regarding the batch quality.

• 3

  Prepare the samples for testing. Use single units of large-volume parenterals for the test. Or use single units of small-volume parenterals with a volume greater than 25 ml. In case of small-volume parenterals with a volume less than 25 ml, combine the contents of 10 or more units to obtain 25 ml or more of sample. Reconstitute dry powders using particle-free water or other appropriate solvents.

• 4

  Calibrate the particle counting apparatus. Use dispersions containing particles of known dimensions from 10 to 25 micrometers, dispersed in water that is particle-free.

• 5

  Clean the laminar air flow cabinet where you will perform the test and the glassware to be used. Ensure there is no chance of particulate contamination from these sources by testing a few samples of particle-free water using the particle counting apparatus. If you find more than 25 particulates of size 10 micrometers or greater, it indicates insufficient cleaning of the area and glassware. Repeat the cleaning, then perform this test again until you obtain satisfactory results.

• 6

  Invert the sample container 20 times to allow mixing of the contents. Clean its external surface with particle-free water. Open the container carefully and keep it undisturbed for two minutes or sonicate to remove gas bubbles.

• 7

  Draw a volume greater than 5 ml and count the particles lying in the 10 to 25 micrometer range. Repeat this with three more portions of the same volume. Ignore the results from the first reading, and calculate the average particle number from the remaining three readings.

• 8

  Filter the sample to be tested through a microporous membrane filter for the microscopic particle count test. Rinse the filter holder walls with particle-free water. Transfer the membrane filter to a Petri dish and leave the lid slightly open to allow it to dry.

• 9

  Keep the Petri dish on the stage of a binocular microscope. Count the number of particles in the 10 to 25 micrometer range.