Particle Condition Change in Emulsion Admixture Evaluated by <i>in Situ</i> Flow Particle Imaging Analysis

Abstract

We evaluated the particle state change in emulsion admixtures using in situ flow particle imaging analysis (FPIA). Ropion® intravenous (flurbiprofen axetil: Ropion®) served as the model emulsion formulation. A binary mixture of Ropion® and normal saline (NS), and a ternary admixture of Ropion®, NS, and Gaster® injection (famotidine: Gaster®) or Primperan® injection (metoclopramide hydrochloride: Primperan®) were prepared and the change in emulsion particle state was analyzed using FPIA under in situ condition. The effect of storage on pH change and the chemical stability of flurbiprofen axetil were also investigated. In Ropion®, various particle images (mean diameter: 2.4 µm) were obtained. From our analysis of changes in scattergrams and particle images, changing behaviors of emulsion particles as a function of storage time depended on the systems of admixture samples. In Ropion®/NS and Ropion®/Gaster®/NS systems, mean particle size and particle number increased with lengthening storage time; however, these values were dramatically increased beyond 6 h in the Ropion®/Primperan®/NS system, corresponding to a decrease in measured pH. The decomposition of flurbiprofen axetil due to incompatibility was not observed in all systems. Detailed information on the change in emulsion particle state was obtained using FPIA, indicating that this method is useful to evaluate state changes in emulsion admixtures under in situ condition.