Impact of Ultrasonic Vibrations on the Stability of Bovhyaluronidase Azoximer in Solution

Changes in the quantitative content and specific activity of hyaluronidase enzyme after ultrasonic treatment of solutions of bovhyaluronidase azoximer were studied. Solutions of the finished dosage form of bovhyaluronidase azoximer (Longidase^® lyophilizate for preparation of solution for injection, 3000 IE) and bovhyaluronidase azoximer drug substance (Longidase^® substance-lyophilizate) were studied. The aim of the study was to determine the effect of ultrasound (US) on the stability of bovhyaluronidase azoximer determined from the measured quantitative content and enzymatic activity of the substance in solution. US at a radiation intensity of 61.4 W/L during treatment in an ultrasonic bath did not significantly affect the quantitative content of the bovhyaluronidase azoximer drug substance in solution, while the decrease in the enzymatic activity of the active substance in Longidase solution after 20 and 30 min of ultrasonic treatment was statistically significant. At the same time, the enzymatic activity of the active substance determined by a biochemical method differed significantly (residual activity from 99.70% to 59.27%) depending on the design features of the nebulizers and the nebulization time after nebulization of the bovhyaluronidase azoximer solution in mesh nebulizers from various manufacturers. Nebulization times of min were least associated with the risk of significant loss of stability of bovhyaluronidase azoximer.