Molecular-properties based formulation guidance tree for amorphous and supersaturable mesoporous silica preparations of poorly soluble compounds

•The manuscript introduces a novel, material-sparing, high-yielding fabrication technique to produce mesoporous silica based amorphous formulations.•The manuscript tests the usability of drug and polymer co-loaded mesoporous silica formulation strategy for a physico-chemically diverse set of compounds. The formulation is well suited for new chemical entities (NCEs) in drug discovery phase to support early PK and toxicology studies.•This manuscript provides fundamental, computational and experimental molecular-properties based formulation guidance tree to a priori predict the possibility of generating amorphous and supersaturable mesoporous silica formulations. This unique and conceptual formulation guidance tree is believed to be extremely beneficial to drug discovery formulators to streamline solubility-enabling formulation efforts. A huge majority of new chemical entities (NCEs) advancing through the drug discovery pipeline often have poor aqueous solubility. This requires formulation scientists to search for solubility enhancement strategies, within the constraints of time and material. To address these challenges, a strategic platform formulation is often required for a rapid compound screening to enable early exploratory PK and toxicology studies. Through this work, we present an option of a material-sparing, high yielding and solubility-enabling amorphous API and HPMCAS-L co-loaded mesoporous silica-based formulation. The usability of this platform formation strategy was assessed for a physico-chemically diverse set of eleven compounds. The formulation approach was successful in stabilizing the model compounds mesoporous silica. Additionally, through the presence of HPMCAS-L, the precipitation risk in supersaturable aqueous environment was significantly reduced. Finally, this manuscript provides fundamental, computational and experimental molecular-properties based formulation guidance tree to a priori gauge the (1) possibility of generating solid-state stable amorphous formulations and (2) sustaining in vitro supersaturation in extreme non-sink dissolution conditions. This unique and conceptual formulation guidance tree is believed to be extremely beneficial to drug discovery formulators to triage NCEs and streamline solubility-enabling formulation efforts.