Title:Formulation Optimization and Characterization of Solid Lipid
Nanoparticles of Apixaban
Volume: 19
Issue: 2
Author(s): Laukik Mulay, Namita Hegde and Abhishek Kanugo*
Affiliation:
- Department of Pharmaceutics, SVKM NMIMS School of Pharmacy and Technology Management, Shirpur, 425405,
Dhule, India
- Department of Pharmaceutical Quality Assurance, SVKM Institute
of Pharmacy, Dhule, 424001, India
Keywords:
Apixaban, Box-behnken design, deep vein thrombosis, DSC, FTIR, hot-homogenization method, solid lipid nanoparticles, SEM.
Abstract:
Background: Unpredictable situations such as clotting of blood, deep vein thrombosis,
and pulmonary embolism arise in the body, which is the leading cause of mortality. Such conditions
generally arise after surgery as well as after treatment with oral anticoagulant agents. Apixaban is a
novel oral anticoagulant widely recommended for the prevention and treatment of strokes and blood
clots suffering from nonvalvular atrial fibrillation by suppressing factor Xa. Apixaban has a log P
of 2.71 with poor solubility and reported maximum bioavailability of approximately 50%.
Objective: Hence, the current research mainly focused on the improvement of solubility, bioavailability,
and therapeutic efficacy of Apixaban via solid lipid nanoparticles (SLN).
Methods: The SLN was developed using the hot-homogenization method using a high-pressure
homogenizer. The drug-lipid compatibility study was assessed by the FTIR, and the thermal analysis
was performed using differential scanning calorimetry (DSC). During the scrutiny of lipids, the
highest solubility of Apixaban was estimated in the glyceryl monostearate, hence selected for the
formulation. Moreover, the colloidal solution was stabilized by the polyethylene glycol 200. The
Design of Expert software (Version 13, Stat-Ease) was implemented for the optimization analysis
by considering the 3-independent factors and 2-dependent parameters. The Patents on the SLN are
Indian 202321053691, U.S. Patent, 10,973,798B2, U.S. Patent, U.S. Patent 2021/0069121A1, U.S.
Patent 2022/0151945A1.
Results: Box-Behnken design was applied along with ANOVA, which showed a p-value less than
0.05 for the dependent parameters such as particle size and entrapment efficiency (p-value: 0.0476
and 0.0379). The optimized batch F10 showed a particle size of 167.1 nm, -19.5 mV zeta potential,
and an entrapment efficiency of 87.32%. The optimized batch F10 was lyophilized and analyzed by
Scanning electron microscopy (SEM), which showed a particle size of 130 nm. The solid powder
was filled into the capsule for oral delivery.
Conclusion: The marked improvement in solubility and bioavailability was achieved with F10-
loaded Apixaban via Solid lipid nanoparticles. Moreover, the sustained released profile also minimizes
the unseen complications that occur due to the clotting of blood.
