Understanding the Concept of Quality by Design (QbD) Strategy

Arteether (ART) is an artemisinin derivative drug used for resistant malaria. It has an oral bioavailability of almost 0.98%. ART-loaded solid lipid nanoparticles (SLNs) were developed with enhanced bioavailability using the quality-by-design approach. ART-loaded SLNs were prepared by the solvent emulsification/evaporation method using the quality-by-design approach. Surfactant concentration and acetone-to-ethanol volume ratio were selected as independent variables, while particle size and entrapment efficiency were selected as responses using central composite design. The produced SLN was lyophilized, and the powdered SLNs were encapsulated in an enteric-coated capsule shell. The particle diameters of all the formulations ranged from 109 to 250 nm, and the entrapment efficiency 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 in preventing 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 were investigated. The bioavailability of ART-loaded SLN was increased to 27.64%. These findings suggest that formulation development, using quality-by-design in the present study, also provides a comprehensive solution for developing an oral formulation of arteether with the desired bioavailability at an industrial scale.