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Optimization of Freeze-Drying Condition of Amikacin Solid Lipid Nanoparticles Using D-Optimal Experimental Design Publisher Pubmed



Varshosaz J1 ; Ghaffari S1 ; Khoshayand MR2 ; Atyabi F2 ; Dehkordi AJ1 ; Kobarfard F3
Authors
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Authors Affiliations
  1. 1. Isfahan University of Medical Sciences, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy, Isfahan, Iran
  2. 2. Tehran University of Medical Science, Tehran, Iran
  3. 3. Shahid Beheshti University of Medical Scinces, Tehran, Iran

Source: Pharmaceutical Development and Technology Published:2012


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±4nm to 23.9±16.7nm; 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 2h. DSC analysis showed chemical interaction between amikacin and cholesterol. © 2012 Informa Healthcare USA, Inc.
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