Refinement of Simvastatin and Nifedipine combined delivery through multivariate conceptualization and optimization of the nanostructured lipid carriers

This study aims to benefit from the capabilities of quality by design (QbD) and design of experiments (DoE) to develop and optimize nanostructured lipid carriers (NLCs) entrapping both Simvastatin (SIM) and Nifedipine (NIF) with the best formulation parameters through screening and optimization stages. NLCs loaded with both SIM and NIF (SIM-NIF-NLCs) were prepared by emulsification evaporation method followed by homogenization. Different factors that may affect the NLCs characteristics were screened using D-optimal design. The effect of the most significant variables on the NLCs quality was optimized using a central composite design. The optimized SIM-NIF-NLCs were characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transforms infrared spectrometry (FTIR). Furthermore, in vitro release and pharmacodynamics of the optimized NLCs formulation were studied. The optimized SIM-NIF-NLCs had a particle size of less than 200 nm and high entrapment efficiency. DSC results showed that SIM and NIF were completely incorporated in the lipids at an amorphous state. The pharmacodynamics study showed that the optimized SIM-NIF-NLCs have a great potential in lowering blood cholesterol levels compared to the individual drug suspensions with a dose reduction of both drugs. This investigation revealed the potential use of both D optimal design and central composite design as valuable tools to recognize the most significant formulation variables as well as to optimize these variables to achieve NLCs with optimal characteristics. [Display omitted]