Particulate matter contamination in injectable drug products, especially in large numbers, can cause harm to patients. Common particulate sources include: solvent impurities, drug precipitates, dust, glass, rubber, environmental contaminants, fibers and other insoluble materials.
The size of particulate matter is an important factor when considering the potential risk to patients. Particles as small as 2 μm in diameter have been associated with microthrombi formation in patients. Dr. Michael Akers with the Food and Drug Administration notes that the smallest capillary blood vessels are considered to have a diameter of approximately 7 μm. Therefore, all particles having a size equal to or greater than 7 μm can conceivably become entrapped in and obstruct capillaries, increasing the potential for adverse effects. Simple visual inspection, which is required for compounded injections, may be adequate for large particles, but is inadequate for smaller particles. The lower limit of visibility of the naked eye is approximately 40 μm. Specialized testing methods are therefore necessary to adequately assess the total particulate burden of injections.
The United States Pharmacopeia establishes procedures and standards to ensure the quality of intravenous injections, including particulate counts. Compounding pharmacists can reduce the incidence of adverse events in patients by assuring the quality of their preparations through filtration of intravenous preparations and analytical testing procedures.
USP Chapter <788> Particulate Matter in Injections recommends two test procedures for determining particulate matter. These two tests are (1) light obscuration particle count test and (2) microscopic particle count test. The two procedures test for particulate matter in preparations and count particles that are equal to or greater than 10 μm and 25 μm.
The USP guidelines limit particulate matter introduced into preparations and into the patient. USP testing methodologies can assure compounding pharmacists of the quality of their preparations and the quantification of subvisible particles. Pharmacists can use these tools to improve patient safety.
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