Comparison of two methods for obtaining size distribution characteristics of particulate matter in large-volume parenterals.

The size distributions of the particulate matter present in six types of large-volume parenteral solutions, as determined by an automatic particle counter and a microscopic counting technique, were compared by plotting log N greater than D versus log D. The resulting data were analyzed individually and also as averages. The data showed a linear relationship between log N greater than D and log D over the 1-100-micron particle-size range, indicating that both methods determine a similar particle-size distribution. The data also indicated that the particle-size distributions were largely independent of the type of solution and obeyed a power law of the form N greater than D = N greater than 1DK. These observations suggest that the major source of contamination is air-borne dust particles, which fall into a solution randomly, and that it may be possible to monitor the smaller, more abundant particles with the automatic particle counter to obtain a rapid estimate of parenteral cleanliness. The automatic particle counter thus appears to be a viable alternative to the microscopic counting technique for assessing the particulate matter content of parenterals.