The Influence of Blonanserin Supersaturation in Liquid and Silica Stabilised Self-Nanoemulsifying Drug Delivery Systems on In Vitro Solubilisation

Reformulating poorly water-soluble drugs as supersaturated lipid-based formulations achieves higher drug loading and potentially improves solubilisation and bioavailability. However, for the weak base blonanserin, silica solidified supersaturated lipid-based formulations have demonstrated reduced in vitro solubilisation compared to their liquid-state counterparts. Therefore, this study aimed to understand the influence of supersaturated drug load on blonanserin solubilisation from liquid and silica solidified supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) during in vitro lipolysis. Stable liquid super-SNEDDS with varying drug loads (90-300% of the equilibrium solubility) were solidified by imbibition into porous silica microparticles (1:1 lipid: silica ratio). In vitro lipolysis revealed greater blonanserin solubilisation from liquid super-SNEDDS compared to solid at equivalent drug saturation levels, owing to strong silica-BLON/lipid interactions, evidenced by a significant decrease in blonanserin solubilisation upon addition of silica to a digesting liquid super-SNEDDS. An increase in solid super-SNEDDS drug loading led to increased solubilisation, owing to the increased drug:silica and drug:lipid ratios. Solidifying SNEDDS with silica enables the fabrication of powdered formulations with higher blonanserin loading and greater stability than liquid super-SNEDDS, however at the expense of drug solubilisation. These competing parameters need careful consideration in designing optimal super-SNEDDS for pre-clinical and clinical application.

Automated summary

Reformulating poorly water-soluble drugs as supersaturated lipid-based formulations can increase drug loading and potentially improve solubilization and bioavailability. However, for the weak base blonanserin, solidified supersaturated lipid-based formulations with silica have shown reduced solubilization compared to their liquid counterparts. This study aimed to understand the influence of supersaturated drug load on blonanserin solubilization from liquid and solid silica-based supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) during in vitro lipolysis.