Emulsion engineering approaches for niclosamide repositioning: A comparative study of shirasu porous glass membrane and high-pressure homogenization techniques

Niclosamide shows therapeutic promise through drug repositioning, but its extremely low aqueous solubility limits oral bioavailability. This study aimed to enhance solubility and absorption by developing an S-SNEDDS and, importantly, by directly comparing two distinct emulsification methods, which has not been previously evaluated for niclosamide. First, a liquid SNEDDS ( L -SNEDDS) composed of corn oil, Kolliphor RH40, and Tween 80 (20:24:56, v/v) was prepared. The L -SNEDDS was then processed using either shirasu porous glass (SPG) membrane emulsification or high-pressure homogenization (HPH). SPG conditions were optimized at a 3.1-µm membrane, 20 kPa pressure, 100 rpm agitation, and 50 min emulsification at 37 °C, while HPH was conducted at 130 kPa for three cycles. Following emulsification, hydrophilic fumed silica was dispersed in each L -SNEDDS and spray-dried to obtain S-SNEDDS. Both formulations showed conversion of niclosamide from crystalline to amorphous. HPH produced smaller and more uniform droplets in L -SNEDDS and resulted in S-SNEDDS with significantly improved solubility and dissolution compared with SPG-treated systems. In rats, S-SNEDDS prepared using SPG and HPH increased oral bioavailability by 64- and 104-fold, respectively, compared to niclosamide powder. Overall, our findings highlight the novel contribution of identifying HPH as a superior emulsification strategy to improve the drug-repositioning potential of niclosamide.