Intratympanic injection of emulsion-like dispersions to co-deliver cinnarizine and morin hydrate-lipoid E80 complex in a rabbit inner ear model.

BACKGROUND: Drug delivery to perilymph after crossing the round window membrane is paramount important for inner ear disease management. Intratympanic (IT) injection of emulsion-like dispersions augments cinnarizine (CNZ) and morin hydrate (MH)-Lipoid E80 complex permeation into perilymph in a healthy rabbit inner ear model. METHODS: A Box-Behnken design (BBD) followed by artificial neural network (ANN)-linked Levenberg - Marquardt (LM) algorithm was used for optimizing the injection formula. Immediately after 30-120 minutes post-IT injections, the concentration levels of CNZ and MH in both perilymph and plasma were monitored. RESULTS: The ANN-linked LM algorithm displayed lower prediction and mean squared errors as well as higher correlation coefficient values for all responses when compared to the corresponding values shown by BBD. The IT injections possessed 156.8 ± 8.5 nm mean particle size, 42.70 ± 4.20 mV zeta potential, >98% CNZ and MH release within 10-20 minutes dissolution in pH 7.4 artificial perilymph solution, >97.26% cell viability in MTT assay and near normal histopathology. The 63.07 ± 23.62 µg/ml CNZ and 82.51 ± 8.33 µg/ml MH were attained in perilymph at 60 minutes post-IT injections. CONCLUSION: The IT-injected formulation can be used to co-deliver two drugs in perilymph for managing inner ear diseases.