Effects of agitation on size distribution of particulate matter in large-volume parenterals.

Abstract

The particle-size distributions of six types of large-volume parenterals subjected to different degrees of agitation were determined using an automatic particle counter. Data acquired from each solution, which had been maintained in a stored condition, subjected to agitation by inverting 20 times, and then mechanically shaken for 30 min, produced a linear relationship between log N greater than D and log D. Both the slope (K) and the number of particles per milliliter exceeding 1 micrometer in diameter (N greater than 1) exhibited a dependence on the degree of agitation. Their combined effect indicates that agitation by 20 hand inversions removed particulate matter from the surface of the container, which increased the total number of particles in solution (greater than 1 micrometer) but did not significantly alter the relative size distribution. Agitation for 30 min, however, disintegrated agglomerates and produced a particle-size distribution with a greatly increased number of particles whose diameters were less than 1 micrometer and a corresponding decrease in the number of particles exceeding 1 micrometer in diameter. The particle-size distribution of a parenteral solution determined by this in situ instrumental method was, therefore, dependent upon the degree of agitation to which the parenteral was subjected prior to examination.