This study aimed to develop a stable nanosuspension of repaglinide and improve its dissolution, using the Nano-precipitation method, involving a different concentration of a stabilizer, different co-stabilizers and different solvents. Employment of a systemic approach to optimize the formulation parameters, including stabilizer concentration, solvent choice and co-stabilizer election. Soluplus® (SOL) was used as the primary stabilizer for this research, polyvinyl alcohol (PVA), poloxamer 188 (PXM 188), tween 80 (TW80), and polyvinyl pyrrolidine (PVP k30) were investigated as co-stabilizers to prevent particle agglomeration and ensure long-term stability. In addition to ethanol as a primary solvent, acetone and chloroform were used for solvent-change assessment. Particle size, polydispersity index (PDI), FTIR study to reveal any interactions and particle morphology using scanning electron microscope, and drug crystallinity and thermal changes were evaluated to assess the physicochemical properties of the nanosuspension. RPG-SOL3 resulted nanoparticle mean size (82.96 nm±3.95) and a PDI of (0.100±0.098). In vitro dissolution studies showed a complete dissolution of the formula and a significant enhancement when compared to RPG drug powder. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed the amorphous nature of optimal RPG nanoparticle. This study successfully develops a stable nanosuspension formulation of repaglinide to improve its dissolution properties. We have achieved a nanosuspension with desirable physicochemical characteristics through systematic optimization of formulation parameters, including selecting stabilizers and co-stabilizers.
