Preparation of compatible formulation of liposomal Amphotericin B with Normal Saline

Abstract

Introduction: Liposomal Amphotericin B (AmB) has represented reduced toxicity compared with plain drug in clinic. However, liposomal AmB percipitates in contact with Normal Saline (NS). Purpose: This project was intended to prepare a compatible formulation of liposomal Amphotericin B with Normal Saline.Methods: Different substances, including DSPE-mPEG 2000, Myrj 52, Poloxamer 408, Poloxamer 188, tween 80, and PEG 2000, were added to modify the liposomal formulation of AmB. Their compatibility with NS was screened at different times. The physicochemical characteristics of the modified liposomes, including Size, Size distribution, Zeta potential, Morphology, Drug loading using direct measurement, Loading capacity, Physicochemical stability, and Drug-lipid interaction studies using FTIR, were investigated. HPLC method was applied for analyzing AmB.Results: In DSPE-mPEG 2000 and Myrj 52 modified formulations, liposomes with acceptable characteristics were obtained. The size range of liposomes was about 132-588 nm and polydispersity ≤0.45. The ZP range lied around –8.8 to -23 mV. The liposomes had spherical shape without aggregation before and after lyophilization. The lyophilized powder of both methods were physically stable for 6-month without changes in color or appearance, however, the liposomal solution of AmB was physically stable for almost two months at 4 °C. After 6-month storage, chemical stability of Myrj 52 and DSPE-mPEG modified liposomes account 89.48% and 92.79%, respectively. FTIR studies revealed the physical loading of AmB without significant chemical interaction between AmB and other components.Conclusion: Different modified liposomal formulations of AmB were prepared with different substances. The formulations prepared with DSPE-mPEG2000 and Myrj 52 can be considered as the most compatible formulations with normal saline serum.