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  • Title: Optimization of freeze-drying condition of amikacin solid lipid nanoparticles using D-optimal experimental design.
    Author: Varshosaz J, Ghaffari S, Khoshayand MR, Atyabi F, Dehkordi AJ, Kobarfard F.
    Journal: Pharm Dev Technol; 2012; 17(2):187-94. PubMed ID: 21047276.
    Abstract:
    Amikacin as an aminoglycoside antibiotic was chosen to be loaded in a cholesterol carrier with nanoparticle size and sustained release profile to increase the dose interval of amikacin and reduce side-effects. To support the stability of solid lipid nanoparticles (SLNs), freeze-drying was suggested. Factors affecting the freeze-drying process in the present study included the type and concentration of cryoprotectants. Pre-freezing temperature effects were also studied on particle size of SLNs of amikacin. In some preliminary experiments, important factors which influenced the particle size of SLNs after lyophilization were selected and a D-optimal design was applied to optimize the freeze-drying conditions in the production of SLNs with minimum particle size growth after freeze-drying. Zeta potential, DSC thermograms, release profiles and morphology of the optimized particles were studied before and after freeze-drying. Results showed sucrose changed the particle size of SLNs of amikacin from 149 ± 4 nm to 23.9 ± 16.7 nm; in that situation, the absolute value of zeta potential changed from 1 ± 0.7 mV to 13 ± 4 mV. The release profiles showed a sustained release behavior of the loaded drug that did not change significantly before and after freeze-drying, but a burst effect was seen after it in the first 2 h. DSC analysis showed chemical interaction between amikacin and cholesterol.
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