Remifentanil and propofol co-loaded nanoemulsion: Formulation development and in vivo pharmacodynamic evaluation

Abstract

Background: The present work is an effort to develop a novel propofol (PPF) and remifentanil (RFT) co-loaded nanoemulsion (NME) for the treatment of anesthetic effects. Methods: The PPF/RFT NME was prepared via the high pressure homogenization method. Its physicochemical properties were assessed to ensure good quality and suitability for i.v. administration. We also studied the in vivo pharmacokinetics and pharmacodynamics of PPF/RFT NME in dogs with an optimized formulation. Results: In this study, the results showed that the mean particle size of PPF/RFT NME was 124.2 nm and the zeta potential was −20.6 mV. In the stability test, the NME maintained a good round shape, and did not demonstrate any significant changes in physicochemical characteristics. In terms of the in vitro release, the early burst release of the NME preparations containing PPF or RFT was ideal in clinical practice, where a loading dose or a rapid onset of the drug was required. Based on histopathological observations, no histological change occurred to the rat organs after the administration of PPF/RFT NME. In regard to pharmacodynamics, compared with the combination group at the same dose, PPF/RFT NME could make animals enter the anesthetic state faster and the anesthetic effects last longer. In addition, vital signs of PPF/RFT NME could be maintained in a good state while better effects were delivered. Conclusions: In this study, PPF and RFT were used to prepare a compound NME. This could reduce the anesthesiologist's administration time and make the anesthesia process more efficient.