Fingolimod SLNs: Preparation, in vitro evaluation and Optimization of lyophilization using D-Optimal Experimental Design

Document Type : Original Article


1 Department of Pharmaceutics, Pharmacy Faculty, Islamic Azad University, Tehran, Iran

2 1Department of Pharmaceutical Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.

3 5Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran


Multiple Sclerosis (MS) is one of the most common neurological disorders diagnosed in young adults. there are no current cures for the disease or its underlying causes, some drugs have been developed that can decrease or delay disease progression. Fingolimod is an immunomodulating drug, mostly used for treating multiple sclerosis (MS). It approximately halves the rate of relapse in relapsing-remitting multiple sclerosis over a two-year period; however, Fingolimod causes a number of off-target effects including cardiovascular complaints. A different delivery method may alleviate some of these effects. Lipid-based nanoparticles containing Fingolimod were prepared using cholesterol as a biocompatible lipid through a high pressure homogenization technique. The physical and chemical properties of the resulting particles, including particle size, zeta potential, morphology, drug-loading capacity and release profile, were investigated. A preferred formula was lyophilized using mannitol as the cryoprotectant. A D-optimal model was used to determine optimum freeze-drying conditions that minimized size enlargement and maximized the zeta potential of the processed particles.
Results: The optimized Fingolimod SLNs are 150 nm in diameter with a Zeta potential of 19 mV. AFM imaging confirms that the particles remain spherical. Fingolimid loading efficiency was found to be 89%, and 85% of the loaded drug was released over 16 days. Results demonstrated that nanotechnology could help to prolong the drug efficacy duration as well could increase compliance of patient to continue MS control, whole life duration.
Conclusion: Sustained release Fingolimod SLNs using cholesterol as the matrix are effective and may provide an alternative to oral drug administration to prolong drug administering intervals and increase chance of treatment following by patients.


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