Development of cinnarizine nanoemulsion for enhanced topical delivery with ex vivo permeation and in vivo pharmacodynamic evaluation

Despite widespread clinical use for vertigo, cinnarizine (CIN) suffers from poor water solubility and unpredictable absorption, limiting its oral bioavailability to approximately 8% when given in liquid dosage forms. We hypothesized that formulating CIN as a nanoemulsion (NE) could enhance skin permeability and enable effective topical delivery for allergic skin conditions, as CIN exhibits antihistamine activity. In this work, we prepared a novel CIN‐NE using low-energy emulsification method. Nanoemulsions were characterized for various parameters, including transmittance, viscosity, refractive index, pH, drug content, mean droplet size, Zeta potential, in vitro drug release, and ex vivo drug permeation. The optimum formula (F19) (30% Smixd of 2:1 with 1% oil) exhibited small nanodroplets (down to 82.03 nm) with a Zeta potential of −16.1 mV and good physical stability in the thermodynamic stability study, which was further formulated as a nanoemulgel to facilitate application. The ex vivo permeation study, using rat skin as a model, showed that NE-F19 and NE-Gel-F19 increased permeability 16- and 5-fold compared with the control, respectively. Additionally, in the in vivo an‐hypersensitivity study, NE-F19 and NE-Gel-F19 effectively suppressed swelling and inflammatory responses.