Analysis of nanoparticles-loaded voriconazole for ophthalmic delivery using statistical experimental design

The present study aims to enhance the solubility of the poorly water-soluble drug voriconazole by preparing nanoparticles (VRZ NPs). Voriconazole nanoparticles were produced by the antisolvent precipitation method. A 23 factorial design was adopted to optimise the variables. Design Expert® software, version 13, was used to determine appropriate concentrations of stabilisers required to form a nanosuspension that would yield optimal particle size (R1), polydispersity index (R2), drug entrapment efficiency (R3), and drug loading (R4). Lyophilised nanoparticles were evaluated by field emission scanning electron microscopy (FESEM) imaging, and powder X-ray diffraction (PXRD) was also conducted. VRZ NPS incorporated into in situ gel (ISG) formed the Nps-ISG formulation, which was further assessed for clarity, pH, gelling capacity, viscosity, and in vitro drug release, and compared with a control drug suspension (CD suspension) and a pure drug in situ gel formulation (D-ISG). Particle sizes ranged from 12.4 to 194nm, PDI from 0 to 0.114, EE% from 48.4% to 95.7%, and DL% from 5.37 to 36.76 for all prepared formulations. FESEM revealed spherical, small particles with a smooth surface, while XRD results demonstrated the amorphous nature of the drug embedded in the NPs. Evaluation of the prepared NPs-ISG showed immediate gelation at 7.12 ± 0.01 seconds and remained gelled for an extended period (+++). The drug content was 99.88 ± 0.47 %, with a low release rate and high viscosity observed. Stability studies indicated low degradation and a maximum shelf life of approximately 1 year. The antisolvent precipitation method proved promising in improving the solubility of voriconazole by producing nanoparticles, and the sustained release rate of the prepared NPs-ISG was concluded.