Intratympanic injections of emulsion-like dispersions to augment cinnarizine amount in a healthy rabbit inner ear model

<b>Aim:</b> To investigate eutectic liquid-based emulsion-like dispersions for intratympanic injections to augment cinnarizine permeability across round window membrane in a healthy rabbit inner ear model. <b>Methods:</b> Two-tier systematic optimization was used to get the injection formula. The drug concentrations in perilymph and plasma were analyzed via. Ultra-performance liquid chromatography-tandem mass spectrometry method after 30-, 60-, 90- and 120-min post intratympanic injection time points in rabbits. <b>Results:</b> A shear-thinning behavior, immediate drug release (∼98.80%, 10 min) and higher cell viability (&gt;97.86%, 24 h) were observed in dispersions. The cinnarizine level of 8168.57 ± 1236.79 ng/ml was observed in perilymph at 30 min post intratympanic injection in rabbits. <b>Conclusion:</b> The emulsion-like dispersions can augment drug permeability through round window membrane. Intratympanic injections containing cinnarizine-loaded emulsion-like dispersions was prepared using camphor-menthol (1:0.97 molar ratio) eutectic liquid. The formula for preparing cinnarizine-loaded emulsion-like dispersions was obtained by applying linear (response surface methodology) and non-linear (artificial neural network) models. The optimized cinnarizine-loaded emulsion-like dispersions was prepared as per the formula suggested by the non-linear model. The MPS, PDI, ZP and drug amount in whole dispersions values of drug-loaded emulsion-like dispersions were 175.40 ± 5.20 nm, 0.245 ± 0.018, 43.20 ± 3.30 mV and 72.37 ± 5.67% w/v, respectively. The DEE, pH and osmolality values of drug-loaded emulsion-like dispersions prepared using the optimized formula were 96.50 ± 0.44%, 7.40 ± 0.07 and 299 ± 42.29 mOsm/kg H2O, respectively. The emulsion-like dispersions were found to be shear thinning (0.1 to 100 s-1 shear rate) and was not affected by coalescence and Ostwald ripening till 90 days at 25°C. The MTT test results performed in L-929 cells displayed cell viability values of more than 97.86% for all tested concentrations of drug-loaded emulsion-like dispersions. The presence of cinnarizine in perilymph and plasma of healthy rabbit inner ear model after intratympanic administration of drug-loaded emulsion-like dispersions was checked using a UPLC-MS/MS bioanalytical method. The intratympanic administration of drug-loaded emulsion-like dispersions displayed cinnarizine concentrations of 470.10 to 8168.57 ng/ml in perilymph for 30–120 min.