Oral Bioavailability and Stability Study of a Self-Emulsifying Drug Delivery System (SEDDS) of Amphotericin B

Abstract

Amphotericin B (AmB) is a poorly water soluble polyene antifungal antibiotic which is negligibly absorbed from the gastro intestinal tract after oral administration. The objective of this research work was to study the oral bioavailability and stability of a self-emulsifying drug delivery system (SEDDS) of amphotericin B (AmB). The SEDDS formulation consisted of glyceryl monooleate, tween 80, polyethylene glycol 400 (PEG 400) and propylene glycol and had AmB content of about 8 mg per ml. The stability of the SEDDS formulation was studied in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) in comparison to pure drug. Oral bioavailability of the SEDDS formulation was studied in rats in comparison to the pure drug. The formulation was filled in two different types of capsule shell, namely HPMC capsule and hard gelatin capsule and stability of the formulation was studied for 3 months. The SEDDS formulation resulted in a mean AUC value of 40.57µg/ml.hr with mean peak plasma concentration of 6.17µg/ml reached after 2 hours after oral administration in rats, whereas concentration of AmB in plasma was not detectable after administration of the pure drug. The formulation filled in hard gelatin capsule shell was physically and chemically stable for more than 3 months under refrigeration (4°C). The study demonstrates that SEDDS approach can be successfully utilized for oral delivery of AmB.