CENTRAL COMPOSITE FACE-CENTERED DESIGN-BASED OPTIMISATION, DEVELOPMENT AND CHARACTERISATION OF FAVIPIRAVIR-LOADED PLGA NANOPARTICLES

Abstract

Objective: The objective of this study is to fabricate favipiravir-loaded PLGA nanoparticulate systems that can increase the solubility along with the sustained release of favipiravir. Methods: The favipiravir-loaded Poly (D, L-lactic-co-glycolide) (PLGA) nanoparticulate systems were prepared by the nanoprecipitation method. A 3-factor, 2-level central composite face-centered design was employed to study the effect of formulation variables having a concentration of PLGA, polyvinyl alcohol (PVA) and stirring rate as critical formulation attributes and particle size, drug entrapment efficiency, and percentage cumulative drug release as critical quality attributes on prepared favipiravir nanoparticles. Drug interaction studies were performed by FTIR and DSC. Surface morphology was analysed by scanning electron microscopy (FEI Quanta 250 FEG, USA). Particle size, zeta potential, and polydispersity index were analysed by the nanoparticle analyser SZ-100 (HORIBA Scientific nanopartica, Japan). In vitro drug release studies were performed using a UV-Visible spectrophotometer at λmax 234 nm. In vitro drug release data obtained was fitted into various mathematical kinetic models. Results: The numerical optimization process predicted the level of PLGA concentration as 69.96 mg, PVA concentration as 4.99%, and stirring rate as 799 rpm for the optimised formulation. The low percentage of relative error for the optimised formulation confirms the validation of the model. The optimised formulation had a 77.65% entrapment efficiency with a particle size of 109.7 nm and the percent cumulative drug release showed 86.46% drug release over 720 min. The drug release was found to follow first-order release kinetics with anomalous non-Fickian diffusion kinetics. Conclusion: Hence, such an attempt at fabrication of favipiravir-loaded PLGA nanoparticulate systems may be useful for sustained release of drug over 720 min.