Intranasal nanoemulsion-based in-situ gel containing dexlansoprazole: formulation development, in-vitro and ex-vivo...

Dexlansoprazole (DXL) is clinically effective in gastroesophageal reflux and ulcer healing, yet its oral bioavailability is compromised by acid instability, poor aqueous solubility, and extensive first-pass metabolism. To address these limitations, an intranasal nanoemulsion-based in situ gel was developed to bypass gastrointestinal and hepatic metabolism and enable rapid systemic absorption via the highly vascularized nasal mucosa. Owing to the BCS Class II nature of DXL, this approach was designed to enhance solubility, prolong nasal residence time, and provide sustained drug release.

DXL-loaded nanoemulsions (NEs) were prepared using Capmul MCM EP as the oil phase, Cremophor EL as the surfactant, and PEG 300 as the co-surfactant by sonication. The NEs were evaluated for various in vitro parameters, in vitro drug release, and ex vivo permeation.

Among all NEs, F3 exhibited optimal characteristics, with a mean droplet size of 40.55 nm, a PDI of 0.374, a zeta potential of -17.70 mV, spherical globules under TEM and the highest cumulative release of 90.02% at 24 h. All NEs displayed significantly enhanced drug release as compared to the drug suspension. Cumulative drug permeation of 90.02 ± 0.565% for F3 and 80.69 ± 0.057% for its in situ gel (F3NEG4) was recorded, with 5.54- and 5.18-fold higher J_ss than the drug suspension, respectively. Additionally, F3 remained physically stable for 3 months at 2-8 °C and 25 ± 5 °C.

The developed DXL-loaded NE improved in vitro dissolution, indicating potential enhancement of bioavailability, which requires confirmation through comprehensive in vivo studies.