Preparation and physicochemical characterization of injectable liposomal amphotericin B

Abstract

Introduction: Liposomal AmB confers improved pharmacokinetic and pharmacodynamic properties besides reduced toxicity compared with the plain drug.Purpose:This project was intended to explore the most appropriate method for preparation of AmB liposomes with acceptable characteristics. Methods:The solubility screening tests in different solvents and pHs were performed. threeliposome preparation methods were examined: ethanol injection, solvent evaporation, and solvent-free method. The physicochemical characteristics of the prepared liposomes including size, size distribution, zeta potential, morphology, drug loading using direct measurement, loading capacity, physico-chemical stability, and drug-lipid interaction studies using FTIR were investigated. HPLC method was applied for analyzing AmB.Results:In all three methods, liposomes with acceptable characteristics were obtained. The size range of liposomes was 150.3to 263.9andpolydispersity ≤0.32. The ZP range lied between -20.39to –25.3mV. The liposomes had spherical shape without aggregation before and after lyophilization. The lowest exposure to NaOH during preparation was considered because of the degradation possibility in basic conditions. The lyophilized powder in solvent-free method was physically stable for 6-month without changes in color or appearance, however, the solution of liposomal AmB was physically stable for almost one month at 4 °C. After 6-month storage, 8% drug loss was achieved, and degradation pattern followed a linear order.FTIR studies revealed the physical loading of AmB without significant interaction between AmB and other components.Conclusion: As a result, AmB-loaded liposomes were prepared in three applicable methods. The solvent-free method can be considered the most economic and environmental friendly.