FORMULATION DEVELOPMENT AND PHARMACOKINETIC STUDIES OF NIRMATRELVIR LOADED SOLID LIPID NANOPARTICLES USING BOX-BEHNKEN DESIGN
DOI:
https://doi.org/10.22159/ijap.2025v17i1.52380Keywords:
Solid lipid nanoparticles, Anti-viral agent, PaxlovidTM, Nirmatrelvir, Compritol888 ATO, Box-behnken design, Risk assessment analysisAbstract
Objective: This study aims to develop a new lipid formulation known as Solid Lipid Nanoparticles (SLNs) to increase the oral bioavailability of Nirmatrelvir (NMT) by facilitating intestinal lymphatic transport. Nirmatrelvir is a crucial antiviral agent utilized for the treatment and prophylaxis of Coronavirus disease 2019 (COVID-19).
Methods: Nirmatrelvir loaded solid lipid nanoparticles (NMT-SLNs) were formulated using the microemulsion technique with compritol 888 ATO, and the optimization of lipid and surfactant concentrations, as well as homogenization time, was achieved through the box-behnken design. The resulting NMT-SLNs underwent evaluation for percentage entrapment efficiency, Particle diameter, Zeta potential, Polydispersity index (PDI), and In vitro drug release studies.
Results: Optimized formulation (NF8), yielded a particle of 183.26±2.12 nm size with a narrow distribution of 0.071±0.004PDI, negative zeta potential of-24.63±1.92 mV, percent entrapment of 86.94±2.08%, and cumulative drug release of 84.42±3.16% over 24 h. Furthermore, solid-state characterization by PXRD, surface morphology assessment by SEM, and an in vivo distribution study employing albino wistar rats were conducted. The findings demonstrated a 10.14-fold increase in relative bioavailability and an 85% enhancement in brain uptake compared to pure NMT solution following oral administration.
Conclusion: This research highlights the potential advantages of solid lipid nanoparticles (SLNs) in enhancing the oral delivery of nirmatrelvir. finally, the study concluded that SLNs serve as a promising vehicle for improving bioavailability and facilitating effective brain delivery.
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