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Nano-structured lipid carriers containing zopiclone were prepared as a targeted drug delivery system to convey zopiclone directly to brain via nasal route. Nano-structured lipid carriers were constructed adopting hot emulsification-ultrasonication method using palmitic acid in place of the solid lipid, cod liver oil as liquid lipid, and poloxamer 407 as a surfactant. A three-factor three-level central composite face-centered design was used to optimize the formulated nano-structured lipid carriers. The independent factors were lipid amount (X₁), surfactant amount (X₂), and sonication time (X₃). The examined responses were entrapment efficiency (EE,Y₁,%), particle size (PS,Y₂,nm), zeta potential(mV), polydispersity index(PDI,Y₃), in vitro release(Q8h,Y₄,%) and dissolution efficiency (DE,Y₅,%). The optimum formula showed high entrapment efficiency of 94.31% ± 2.44, in vitro drug release of 83.89% ± 1.77 with …