Enhanced Bioavailability of Nadolol via Cinnamon Oil-Based Microemulsions: Formulation, Characterization, Cell Culture, and In Situ Intestinal Perfusion Studies

Abstract

The purpose of this study was to develop and evaluate novel nadolol (NDL)-loaded microemulsions for oral application. Microemulsions were prepared using a pseudoternary phase diagram through the aqueous titration method. The optimum formulation constituted a mixture of cinnamon oil as the oil phase, Tween 20 as the surfactant, propylene glycol:ethanol as cosurfactants, and distilled water as the water phase. The selected formulation was loaded with 4% NDL. Droplet size, polydispersity index (PDI), ζ-potential, conductivity, pH, refractive index, viscosity, thermodynamic stability, storage stability, and in vitro drug release were evaluated in characterization studies. Cell culture and in situ single-pass intestinal perfusion (SPIP) were investigated. Cell studies were performed in order to understand the cytocompatibility by using the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) method and the permeation of NDL by using the Caco-2 cell line. To estimate the permeability values, SPIP was carried out with female Sprague–Dawley rats. An ideal NDL-loaded microemulsion formulation showed an average 1.01 ± 0.07 nm droplet size, 0.46 ± 0.04 PDI, and −10.26 ± 0.87 mV ζ-potential. pH, viscosity, conductivity, and refractive index values of an ideal NDL-loaded formulation were found to be 5.88 ± 0.02, 76.67 ± 5.77 cP, 201.70 ± 0.00 μS/cm, and 1.42 ± 0.00, respectively. In the SPIP study, an ideal NDL-loaded microemulsion formulation was found to have 5.826 times higher NDL permeability compared to a pure NDL solution, and the estimated fraction of the substance absorbed in humans was determined to be 39.821 ± 9.202%. It was found to have suitable thermodynamic and storage stability. This study showed that NDL-loaded microemulsions can serve as promising oral drug delivery systems for antihypertensive purposes. The developed NDL-loaded microemulsion significantly improved permeability and predicted oral absorption while maintaining safety, indicating strong potential as an effective oral formulation. These results suggest that it may enhance therapeutic outcomes in hypertension, although further in vivo and clinical studies are needed.