Implementing Quality by Design (Qbd) Strategy for Optimization of lyophilized Solid Lipid Nanoparticles to Boost Oral Bioavailability of antimalarial drug

Abstract

Background: Arteether (ART) is artemisinin derivatives drug used for resistant malaria. It has oral bioavailability of almost 0.98 %. AIM: ART loaded solid lipid nanoparticles (SLN) were developed with enhanced bioavailability using Quality by Design approach. Methodology: ART loaded SLNs were prepared by solvent emulsification/evaporation method using Quality by Design approach. Surfactant concentration and acetone to ethanol volume ratio were selected as independent variable while particle size and entrapment efficiency was selected as responses using central composite design. Result: The produced SLN were lyophilized and the powdered SLNs was encapsulated in an enteric coated capsule shell. The particle diameters of all the formulations were between 109 and 250 nm, and the entrapment effectiveness was 93.7 %. The XRD spectrum revealed that the ART was in amorphous form. The ART-SLNs release pattern revealed that ART was released in a slow yet time-dependent manner, which seems beneficial to prevent it from acid degradation. The permeability of ART containing formulations was investigated using the Franz diffusion cell technique. The concentration of ART employing ART-SLN to pure ART in the pig's intestine was nearly 7.1 fold enhanced. The pharmacokinetics of ART-SLN administered orally to rabbit models was investigated. The bioavailability of ART-loaded SLN was increased to 27.64%. Conclusion: These findings suggest that formulation development by using quality-by-design in present study also provide a comprehensive solution to develop oral formulation of arteether with desired bioavailability at industrial scale.