Solid spontaneous emulsifying formulations containing mucolytic agents to enhance nasal mucosal permeability of poorly water-soluble drugs

Intranasal administration is a highly effective route for local and systemic drug delivery, with high drug permeability through the nasal mucosa. Rapid symptom relief is expected given its low invasiveness and rapid onset of action. However, many therapeutic drugs are poorly soluble and do not readily penetrate the mucin layer (mucus layer) on the mucosal surface, and mucociliary clearance is a major challenge. In this study, we aimed to develop a porous solid formulation that combines spontaneous emulsifying properties for dispersing poorly soluble drugs with a powder property that is expected to have mucosal retention. Regardless of the presence or absence of additives, Eudragit ® L 100 porous particles impregnated with an oil phase containing a hydrophilic surfactant maintained their shape, rapidly emulsified, and formed fine emulsions. Furthermore, the addition of hydrophilic additives and mucolytic agents (D-mannitol or sodium chloride) increased the solubility and osmotic pressure of the porous particles, promoted emulsification, decreased mucus viscosity, and facilitated the diffusion of the emulsions through the mucus layer. This effect was particularly pronounced with D-mannitol. In conclusion, by combining mucolytic agents with the spontaneously emulsifying formulation, we developed a powder formulation that simultaneously achieves rapid emulsification on the mucosal surface and diffusion into the mucin layer. Our findings provide a reference for future research that will enable more efficient delivery of drugs to epithelial cells, thereby improving drug absorption through the mucosa. • A spontaneous emulsifying formulation was developed for intranasal drug delivery. • Tween 80 affected the particle size and surface potential of the formed emulsions. • Formulations with mucolytic agents improved diffusion through the mucus layer. • D-mannitol of the mucolytic agent enhanced even the spontaneous emulsification.