The current study aimed to systematically develop stable parenteral itraconazole liposomes using a statistical design of experiment approach. A 32 full factorial design was constructed to prepare nine liposomal batches by varying concentrations of hydrophobic lipid (hydrogenated soy phosphatidylcholine (HSPC) or distearoylphosphatidylcholine (DSPC) and cholesterol. Liposomes were formulated employing spray drying and lyophilization techniques. Itraconazole content was quantified using a validated UV spectrophotometric method. Fourier transform infrared spectroscopy (FTIR) confirmed no interactions between the drug and excipients. The formulated liposomes were evaluated for critical attributes including pH, drug loading efficiency, vesicle size, zeta potential and in vitro drug release. Entrapment efficiencies ranged from 33-95% for HSPC liposomes and 26-90% for DSPC liposomes. Optimal batches LH5 and LD5 exhibited particle size less than 150nm, zeta potential greater than -30mV and sustained release for 24 hours. Statistical analysis suggested the liposomal attributes were influenced by lipid composition and concentrations. The developed liposomes demonstrated desired characteristics for parenteral itraconazole delivery.