Application of Design of Experiment in the Optimization of Apixaban-Loaded Solid Lipid Nanoparticles: In Vitro and In Vivo Evaluation

Solid lipid nanoparticles (SLnPs) are usually utilized as lipid-based formulations for enhancing oral bioavailability of BCS class IV drugs. Accordingly, the objective of this work was to investigate the effect of formulation and processing variables on the properties of the developed SLnPs for oral delivery of apixaban. Randomized full factorial design (2⁴) was employed for optimization of SLnPs. With two levels for each independent variable, four factors comprising both formulations and processing factors were chosen: the GMS content (A), the Tween 80 content (B), the homogenization time (C), and the content of poloxamer 188 used (D). The modified hot homogenization and sonication method was employed in the formulation of solid lipid nanoparticles loaded with apixaban (APX-SLnPs). The size of APX-SLnPs formulations was measured to lie between 116.7 and 1866 nm, polydispersity index ranged from 0.385 to 1, and zeta potential was discovered to be in the range of − 12.6 to − 38.6 mV. The entrapping efficiency of APX-SLnPs formulations was found to be in the range of 22.8 to 96.7%. The optimized formulation was evaluated in vivo after oral administration to rats. Oral administration of APX-SLnPs resulted in significant prolongation in bleeding time compared with both positive and negative control. This indicates the ability of this system to enhance drug therapeutic effect either by increasing intestinal absorption or trans-lymphatic transport. So, this study highlighted the capability of SLnPs to boost the pharmacological effect of apixaban.

Materials

Apixaban (APX) was obtained as a gift from ATCO Pharma for pharmaceutical industries, Egypt. Glycerol mono stearate (GMS) which is a solid lipid was obtained from El Qahera for Pharmaceutical & Chemical Industries, Egypt. The surfactants that were utilized in this work included Tween 80 from El-Nasr Pharmaceutical Chemical Co., Egypt, Poloxamer 188 (Pluronic F68) from Amoun Pharmaceutical Co., Egypt, and Poloxamer 407 (Pluronic F127) from Sigma for Pharmaceutical Industries. Ketamine had been received as a gift from EIPICO for Pharmaceutical Industries. Acetonitrile (HPLC grade) was purchased from SDFCL (S D Fine-Chem Limited, Mumbai, India). Disodium hydrogen phosphate was acquired from Lanxess AG, India.

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Ramadan, S.E., El-Gizawy, S.A., Osman, M.A. et al. Application of Design of Experiment in the Optimization of Apixaban-Loaded Solid Lipid Nanoparticles: In Vitro and In Vivo Evaluation. AAPS PharmSciTech 24, 167 (2023).
https://doi.org/10.1208/s12249-023-02628-2