Evaluation of a simple method for visual detection of microprecipitates in blends of parenteral drug solutions using...

The formation of microprecipitates (sub visible particles) is a critical factor when blending parenteral drug solutions prior to or during intravenous administration to a patient. In cases where compatibility is not documented, analytical screening of such mixtures for physical incompatibility would give a safer foundation for secure administration of such blends to patients. The aim of this article is to report our experiences with visual screening using a focused (Tyndall) light beam for the detection of micro precipitates within blends of drug solutions, a method which may be used in any hospital pharmacy without use of advanced analytical instrumentation. A selection of clinically applied drug solutions was tested for precipitation upon blending in a proportion of 1:1. In order to reduce potential background particle burden, the solutions were filtered through 0.2 micrometer pore size filters prior to mixing. To detect potential precipitation, the solutions were visually inspected using two different types of focused light beams, a 75-watt white, focused light source and a HeNe pocket laser-pointer, for light scattering. For comparison, a light obscuration particle counter test was performed as described in the European Pharmacopeia. An experimental set-up is described, and a detailed protocol is suggested for a method able to detect micro precipitates in drug solution blends by using focused (Tyndall) light. The performance of this method for selected blends is reported in comparison to the Pharmacopeial light obscuration particle count test. Despite the fact that visual inspection using Tyndall light is a simple and low-cost method, it was found sensitive for detecting minute amounts of sub visible particles with detection sensitivity close to the light obscuration particle counting limits stated by the European Pharmacopeia. In cases where an electronic particle counter is not accessible, a sensitive warning signal may be obtained from this approach indicating that it is not advisable to mix such solutions. Certain drug solutions, as well as their actual concentrations, can have an effect on precipitation, and, therefore, should be recorded in mixing tables for clinical use. The Tyndall method employed here may represent an important tool for improving the quality of decisions on whether to give two solutions simultaneously to a patient.