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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Physical Chemistry

Background:

• Amphotericin B (AmB) is a vital antifungal and antileishmanial drug.
• Lipid-based systems, such as microemulsions (ME), enhance AmB's therapeutic index by reducing nephrotoxicity.
• The complex nature of ME hinders simple modeling of AmB degradation.

Purpose of the Study:

• To establish a degradation scheme and mathematical model for AmB within a microemulsion (ME).
• To investigate AmB degradation pathways in lipidic, aqueous, and micellar environments.
• To quantify AmB degradation kinetics in ME under dark conditions.

Main Methods:

• Literature review of AmB degradation in various media.
• Experimental investigation of interfacial degradation using micellar formulations.
• Quantification of AmB using High-Performance Liquid Chromatography (HPLC).
• Development of a multi-pathway mathematical model for AmB degradation.

Main Results:

• Oxidation, influenced by surfactant-induced aggregation, is the primary degradation pathway in micelles.
• A comprehensive degradation scheme considering lipidic, aqueous, and micellar phases was proposed.
• A complex multi-pathway mathematical model accurately described experimental AmB degradation data in ME.
• Kinetic constants for AmB degradation in ME were determined, highlighting the roles of aggregation and oxidation.

Conclusions:

• The developed mathematical model accurately describes non-linear AmB degradation in liquid lipid-based dispersions.
• This work provides a foundation for understanding and predicting AmB stability in advanced drug delivery systems.
• The findings could enhance the market viability of AmB formulations in microemulsions.