Design and In Vitro Evaluation of Intranasal Diazepam for Treating Acute Repetitive Seizures: a Technical Note

This study aimed to develop and characterize a novel microemulsion-based intranasal diazepam for treating acute repetitive seizures (ARS). The solubility of diazepam was obtained in different solvents. An oil in water microemulsion was prepared with castor oil as oil phase, polyethylene glycol monostearate as surfactant, ethanol as cosurfactant, and water. The formulation was further evaluated for droplet size, zeta potential, pH, in vitro drug release, morphology using transmission electron microscopy (TEM), thermal property using differential scanning calorimetry (DSC), and stability and toxicity in the bovine nasal mucosa. The developed o/w microemulsion system exhibited a droplet size of 51.23 nm with a neutral zeta potential. The pH of microemulsion was close to the pH of nasal secretions. The TEM image revealed the spherical droplet shape, and the DSC thermogram showed conversion of diazepam from a crystalline form to an amorphous/molecular dispersion form. Histological evaluation of the microemulsion showed an intact bovine nasal mucosa without any signs of toxicity and was found to be stable at 25 °C for up to 3 months. To conclude, the reported microemulsion could be further explored as an alternative for treating ARS.