Bioavailability Enhancement of Polymyxin B With Novel Drug Delivery: Development and Optimization Using Quality-by-Design Approach

Polymyxin-B (Poly-B) is an effective antibiotic used to treat infections mainly caused due to sensitive gram-negative bacteria. They belong to the group of cyclic peptide antibiotics and are minimally absorbed from the gastrointestinal tract. This arises the need for bioavailability enhancement and is achieved in the present case using niosomes as carrier system. The Poly-B niosomes had been developed using Span 60 and cholesterol while optimization is achieved with quality-by-design (QBD) approach. In this QBD approach, 3 independent variables (Span 60: cholesterol, volume of phosphate-buffered saline [%], and amount of drug [mg]) each at 3 levels were studied. A total of 17 runs were suggested by the model which was further analyzed by optimizing 3 different responses (particle size, zeta potential, and entrapment efficiency [EE%]). The results had clearly shown that the optimum formulation selected by QBD was based on the criteria of attaining the maximum value of EE% and low value of size and zeta potential. Poly-B niosomes were further examined by in vitro antifungal, rat creatinine, and cytotoxicity assay. The pharmacokinetics and scintigraphy studies were also performed for in vivo behavior of Poly-B. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.