QbD-driven development and evaluation of nanostructured lipid carriers (NLCs) of Olmesartan medoxomil employing multivariate statistical techniques

<p><b>Purpose:</b> This research work entails quality by design (QbD)-based systematic development of nanostructured lipid carriers (NLCs) of Olmesartan medoxomil (OLM) with improved biopharmaceutical attributes.</p> <p><b>Methods:</b> Quality target product profile (QTPP) was defined and critical quality attributes (CQAs) were earmarked. Solubility of drug was performed in various lipids for screening of them. NLCs were prepared by hot-microemulsion method using solid lipids, liquid lipids and surfactants with maximal solubility. Failure mode and effect analysis (FMEA) was carried out for identifying high risk formulation and process parameters. Further, principal component analysis (PCA) was applied on high risk parameters for evaluating the effect of type and concentration of lipids and surfactants on CQAs. Further, systematic optimization of critical material attributes (CMAs) was carried out using face centered cubic design and optimized formulation was identified in the design space.</p> <p><b>Results:</b> FMEA and PCA suggested suitability of stearic acid, oleic acid and Tween 80 as the CMAs for NLCs. Response surface optimization helped in identifying the optimized NLC formulation with particle size ∼250 nm, zeta potential <25 mV, entrapment efficiency >75%, <i>in vitro</i> drug release >80% within 6 h. Release kinetic modeling indicated drug release through Fickian-diffusion mechanism.</p> <p><b>Conclusions:</b> Overall, these studies indicated successful development of NLCs using multivariate statistical approaches for improved product and process understanding.</p>