Particulate Matter in Parenteral Products: A Review

Steven J. Borchert; Amy Abe; D. Scott Aldrich; Lloyd E. Fox; James E. Freeman; Robert D. White

Abstract

Particulate matter in parenteral products is a complex subject. This article contains a discussion of several aspects of this topic including the use and limitations of the inspection and counting techniques for visible and subvisible particles, the identification of particles, and the elucidation of sources, mechanisms of formation, and particulate reduction techniques. Two significantly different approaches, human and machine inspection, have been used to detect visible particulate matter in parenteral products. A description of both methods is given along with a discussion of their typical performance characteristics. Criteria for comparison of different visual inspection systems are also presented. A variety of methods have been utilized for the measurement of subvisible particulate matter, including microscopic, electrical zone-sensing, light blockage, light scattering, and holographic techniques. Each of these particle counting methods is described. In addition, the factors that affect the measurement of subvisible particulate matter are discussed. An approach to particle identification is outlined. General comments concerning the analysis of particulate matter in parenteral products are discussed along with a description of various particle identification techniques and several examples illustrating how the methods have been applied. In particular, the techniques that are presented include light microscopy, atomic spectroscopic methods (SEM/EDXRA, electron microprobe, ESCA, and Auger electron spectroscopy), molecular spectroscopic techniques (infrared spectroscopy, Raman spectroscopy, and mass spectrometry), and chromatography. Finally, sources of particulate matter including packaging materials, manufacturing variables, formulation components, and miscellaneous factors are reviewed. The different mechanisms of particle formation, namely, direct contamination, precipitation and agglomeration are discussed. Representative examples of particulate reduction steps are presented.

PDA members receive access to all articles published in the current year and previous volume year. Institutional subscribers received access to all content. Log in below to receive access to this article if you are either of these.

If you are neither or you are a PDA member trying to access an article outside of your membership license, then you must purchase access to this article (below). If you do not have a username or password for JPST, you will be required to create an account prior to purchasing.

Full issue PDFs are for PDA members only.

Note to pda.org users

The PDA and PDA bookstore websites (www.pda.org and www.pda.org/bookstore) are separate websites from the PDA JPST website. When you first join PDA, your initial UserID and Password are sent to HighWirePress to create your PDA JPST account. Subsequent UserrID and Password changes required at the PDA websites will not pass on to PDA JPST and vice versa. If you forget your PDA JPST UserID and/or Password, you can request help to retrieve UserID and reset Password below.