Preparation and characterization of nanosponge-based systems to enhance the solubility of poorly water-soluble drugs

This study reports the formulation and optimization of olanzapine-loaded ethylcellulose-based nanosponges using a Design of Experiments (DoE) approach and desirability-function analysis, varying ethylcellulose (EC), polyvinyl alcohol (PVA) and stirring speed. Formulations were characterized for particle size (240.7–853.9 nm), polydispersity index (PDI, 0.343–0.713), and zeta potential (−22.8 to −39.3 mV). Production yields ranged from 3.88% to 49.31%, while entrapment efficiency (EE%) varied between 25.73% and 77.87%; the optimized batch (Run 17) showed an intermediate particle size (447.8 nm), PDI 0.46, zeta −34.8 mV, production yield 35.48% and EE 72.16±3,6%. Scanning Electron Microscope (SEM), Fourrier Transform İR Spectrometer (FTIR), Dıfferential Scanning Calorimetry (DSC) and X- Ray Crystallography (XRD) analyses confirmed porous nanosponge morphology, successful drug incorporation and partial conversion of olanzapine from crystalline to a more amorphous/molecularly dispersed state within the polymer matrix. Analytical trends indicated that higher EC combined with adequate PVA and appropriate stirring speeds favored matrix formation and enhanced drug entrapment, whereas extreme polymer or RPM settings reduced performance. In Vitro dissolution studies revealed pH-dependent release: sustained release at pH 1.2, comparable release at pH 6.8, and significantly enhanced cumulative release from nanosponges versus pure olanzapine at pH 7.4. Overall, ethylcellulose-based nanosponges markedly improved olanzapine dissolution under physiological conditions and the optimized formulation demonstrates suitable properties for scale-up and further In Vivo evaluation. Keywords: Olanzapine, Nanosponges, SEM, FTIR, DSC, XRD, Entrapment Efficiency, In Vitro, Drug Delivery.