Development of Injectable Itraconazole Liposomal Formulation by Lyophilization Technique: Optimization, Freeze-Drying, and Stability Analysis

Abstract

Objective: The aim of this study was to develop an injectable itraconazole liposomal formula using freeze-drying.

Methods: Synthetic lipids, hydrogenated soy phosphatidylcholine (HSPC) and Di-stearoyl phosphatidylcholine (DSPC), were utilized to form liposomes, which were optimized based on characteristics like drug release. To ensure stability and efficacy upon intravenous administration, freeze-drying was employed. This process involved freezing, primary and secondary drying, vacuum break, stoppering, and sealing. Parameters were established using theoretical considerations and freeze-drying microscopy. Collapse temperature (Tc) was determined, that helps in marking freeze-dried product structural loss.

Results: Notably, LH5 and LD5 formulations displayed optimal attributes including size, entrapment efficiency, pH, zeta potential, and 24-hour drug release. LH5 liposomes began collapsing at -28°C and fully collapsed at -22°C. LD5 liposomes showed similar behavior with collapse temperatures of -30°C and -24°C. Stability studies on itraconazole liposomal dispersion (LH5) pre-freeze-drying affirmed 24-hour stability at 25°C, evident from appearance and assay results.

Conclusion: In conclusion, freeze-drying successfully crafted stable, optimized itraconazole liposomal forms. This preserved liposomal traits and drug content. Stability studies confirmed pre-unstable liposomal dispersion processing feasibility. These results confirm the viability of stable injectable itraconazole liposomal formulations for pharmaceutical use.