Professor University of Copenhagen Copenhagen OE, Hovedstaden, Denmark
Amphotericin B (AmB), an anti-fungal drug on WHOs list of essential medicines, is only available for IV infusion, which complicates its accessibility in developing countries. AmB is unstable and has low permeability, and very low solubility in both water and lipids. With the aim of enabling oral AmB delivery, we investigated the possibility of loading AmB into self-nanoemulsifying drug delivery systems (SNEDDS) as an AmB-monoacylphoshatidylcholine complex (APC). Different ratios of AmB and monoacylphoshatidylcholine were tested and the optimal ratio identified. The APC-SNEDDS approach resulted in a >33 times higher loading of AmB in SNEDDS, as compared to pure AmB in SNEDDS, and was stable without crystallization. In vitro studies, simulating rat gastrointestinal digestion, revealed that 30% of the AmB in APC-SNEDDS was solubilized, while the rest precipitated in the amorphous form.In vitro digestion of the APC lead to precipitation of all AmB. Oral dosing to rats resulted in a significantly increased Cmax and AUC0-24h for the APC-SNEDDS compared to APC and AmB in SNEDDS. Thus, the APC-SNEDDS concept is a promising approach to enable oral delivery of AmB and other drugs with low lipid solubility.
Learning Objectives:
Apply phospholipid complexes for making it possible to load non-lipophilic drug into lipid-based drug delivery systems
Describe in vitro and in vivo characterization methods for lipid-based drug delivery systems
Understand the use of Design of Experiment for Development of Self-nanoemulsifying Drug Delivery Systems
