Formulation Design and Optimization for the Improvement of Nystatin-Loaded Lipid Intravenous Emulsion

Nystatin (NYS) is a polyene macrolide with broad antifungal spectrum restricted to topical use owing to its toxicity upon systemic administration. The aims of this work were the design, development, and optimization of NYS-loaded lipid emulsion for intravenous administration. A closed circuit system was designed to apply ultrasound during the elaboration of the lipid intravenous emulsions (LIEs). Additionally, a comparison with the commercially available Intralipid((R)) 20% was also performed. Manufacturing conditions were optimized by factorial design. Formulations were evaluated in terms of physicochemical parameters, stability, release profile, and antimicrobial activity. The average droplet size, polydispersity index, zeta-potential, pH, and volume distribution values ranged between 192.5 and 143.0nm, 0.170 and 0.135, -46 and -44mV, 7.11 and 7.53, 580 and 670nm, respectively. The selected NYS-loaded LIE (NYS-LIE54) consisted of soybean oil (30%), soybean lecithin (2%), solutol HS (R) 15 (4%), and glycerol (2.25%) was stable for at least 60 days. In vitro drug release studies of this formulation suggested a sustained-release profile. Equally, NYS-LIE54 showed the best antimicrobial activity being higher than the free drug. Thus, it could be a promising drug delivery system to treat systemic fungal infections. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:4015-4023, 2013