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The strategies to avoid blood brain barrier are been explored to improve brain targeting therapeutics in order to ensure potential prospects of nose to brain delivery. In this research work, Buspirone (BUS) loaded solid lipid nanoparticles (SLNs) for nose to brain delivery were prepared by solvent free technique and optimized by three factors and three levels Box- Behnken design. The three independent variables viz, drug (BUS) to lipid (Compritol® 888 ATO) ratio (labeled A), surfactant concentration (tween 80+ poloxamer, 2:1- labeled B) and sonication time (labeled C) were selected in range of 1:3–1:5, 1–2% and 5–15 min respectively. Their influences on particle size (nm, labeled Y1), Polydispersity index (PDI, labeled Y2) and % entrapment efficiency (labeled Y3) were observed. Optimized batch (B-OP3) showed spherical morphology possessing the value of particle size, PDI, zeta potential, entrapment efficiency …