Development and Validation of a Procedure for Subvisible Particles Determination in Water for Injections by the Coulter Principle (Electrical Sensing Zone Method)

Abstract

Water for injections is one of the most popular diluents used for preparation of parenteral dosage forms. The European Pharmacopoeia recommends two methods for the determination of subvisible particulate matter: Light Obscuration Particle Count Test and Microscopic Particle Count Test. The Russian Pharmacopoeia, 13th ed., additionally allows for the use of the Coulter principle (Electrical Sensing Zone method). Thus, a procedure had to be developed for subvisible particles determination in water for injections based on the Coulter principle (hereinafter — procedure). The article presents the results of development and validation of the procedure, i.e. the characteristics of accuracy, dilutional linearity, ruggedness in terms of the time factor, and repeatability for particles more than 10 μm in size. The results of subvisible particles determination obtained with the help of the developed procedure based on the Coulter principle were compared to the results obtained with the help of the light obscuration particle count test. The accuracy of the developed procedure was supported by the statistical insignificance of the differences between the obtained results. The values of ruggedness in terms of the time factor (NMT 14 %) and repeatability (NMT 15 %) did not exceed the established acceptance criterion which is equal to the acceptable limit of the instrument error for particle count in the tested samples (20 %). The dilutional linearity of the procedure was demonstrated (coefficient of determination R2 = 0.999). The results obtained during the validation studies support the possibility of using the Coulter principle for the assessment of subvisible particles in water for injections.