Fabrication of efavirenz loaded nano-formulation using quality by design (QbD) based approach: Exploring characterizations and in vivo safety

Abstract

Quality by design (QbD) approach was practically applied in fabrication of nanostructured lipid carrier (NLC) encapsulating efavirenz (EF) to ensure the quality in product. Initially, risk factors were categorized based on risk priority number (RPN) using risk identification and assessment tools. A central composite rotatable design (CCRD) was employed to assess the influence of critical process parameter (CPP) (pressure of high pressure homogenizer) and critical material attributes (CMAs) (combination of solid lipid and oil; combination of stabilizers) on responses such as particle size, dispersity and entrapment efficiency. ANOVA was applied to evaluate the data for confirmation of statistical significance (p < 0.05). The optimum formulation was decided by setting criteria of responses to achieve desired quality product. This formulation was subsequently lyophilized to evaluate solid state characterization. TEM shows spherical particle shape of NLC. The transformation in amorphous state of NLC from crystalline EF was observed by DSC and PXRD. Lack of molecular interactions and intermolecular hydrogen bonding with lipidic atmosphere revealed by FTIR and 1HNMR respectively. In vitro drug release 91.21% was obtained at the end of 24 h with Higuchi-matrix mechanism. In vivo pharmacokinetic studies improved relative bioavailability 2.95 fold with lower liver toxicity of EF encapsulated in NLC. In conclusion, QbD based approach clearly proved its usefulness to build quality in product resulting high drug encapsulated potential nanocarrier to enhance bioavailability and confirms safety of EF-NLC with promising acceptable criteria.