Optimization of freeze-drying condition of amikacin solid lipid nanoparticles using D-optimal experimental design

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.

Keywords::

• Particle size
• D-optimal
• cryoprotectant
• stability
• freeze-drying

Acknowledgements

The authors would like to thank the Research Vice Chancellor of Isfahan University of Medical Sciences for financial support of this project. Special thanks to Dr Mohammad Ali Faramarzi to provide us with a −80°C deep freezer. The technical assistance of Mrs Sepideh Norouzi, Mrs Hajar Shaabani and Mr Reza Jafarian is appreciated. The authors also thank Mr Rezae for SEM pictures and Mrs Yousefi for improving the English of the manuscript.

Declaration of interest

Financial support for this project was given by the Isfahan University of Medical Sciences, grant number 387317. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.