Physicochemical compatibility investigation of ciprofol injection with eight cardiovascular drugs during simulated Y-site administration

Abstract

The intravenous pharmacotherapy in patients with critically ill and perioperative intravenous anesthesia is extremely challenging due to the large number of drugs administered. In-line incompatibility remains a significant safety concern. We therefore evaluated the physico- chemical compatibility of combinations of ciprofol injection with cardiovascular drugs during simulated Y-site administration frequently used in intensive care unit setting or intravenous anesthesia. Ciprofol injection was mixed with clinical concentrations of dopamine, sodium nitroprusside, dobutamine, phentolamine, papaverine, nitroglycerin, metaraminol and methoxamine solution at a 1:1 vol ratio under ambient conditions (25 ± 1 °C). Physicochemical compatibility changes in appearance, pH values, Zeta potential, particle size/polydispersity index (PDI), osmotic pressure, and relative percentage content are observed at predetermined time points (0, 2, 4, 6, and 8 h). During the 8-hour study period, the pH values change of all drug mixture remained within ±0.4. The relative drug concentration was maintained between 95 % and 105 %. The mean particle size was in the range of 200 to 220 nm, with a PDI below 0.2. Osmotic pressure changes were consistently <6 %. Notably, the Zeta potential of the metaraminol-ciprofol mixture exhibited a variation exceeding ±10 mV. Microscopic imaging analysis showed that the droplet sizes of dopamine-ciprofol, metaraminol-ciprofol, and papaverine-ciprofol mixtures, increased significantly. Based on this studies, ciprofol injection demonstrated compatibility and stability when administered via Y-site infusion with sodium nitroprusside, dobutamine, methoxamine, phentolamine, and nitroglycerin for up to 8 h at room temperature. However, the combination of ciprofol with dopamine, metaraminol, or papaverine was incompatibility during infusion. pH is a significant factor that could potentially influence the stability and compatibility of the combinations. Clinical strategies such as the use of inline filters and post-infusion irrigation tubes can prevent these risks.