Characterizing the Complex Multi-Step Degradation Kinetics of Amphotericin B in a Microemulsified Drug Delivery System

Abstract

Amphotericin B (AmB), a potent amphiphilic drug with antifungal and antileishmanial properties, exhibits reduced nephrotoxicity when delivered via lipid-based systems like microemulsions (ME). However, the complexity of these multi-phasic systems challenges the use of simple schemes and models for describing AmB degradation. The aim of this study was to establish a degradation scheme and model for AmB within a ME, alongside a control micellar formulation. AmB degradation pathways and models in both lipidic and aqueous systems were evaluated based on prior research. Experimental investigations into interface degradation pathways were conducted using a micellar approach. High-Performance Liquid Chromatography (HPLC) was employed for AmB quantification. Oxidation emerges as the principal degradation pathway within micelles, dependent on surfactant-induced aggregation. Considering AmB's behavior in distinct media (lipidic, aqueous, and micellar), an empirical degradation scheme is proposed, translated into a complex multi-pathway mathematical model capable of describing experimental data on AmB degradation in ME under dark conditions. Aggregation and oxidation played significant roles, and kinetic constants were calculated for AmB in ME. The model presented here represents a significant step toward accurately describing the non-linear degradation of AmB in prospective liquid lipid-based dispersions, potentially advancing its market prospects.