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

Abstract

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. © 2026 Elsevier B.V.