In Vivo Evaluation of Palbociclib Loaded Solid Lipid Nanoparticles by Design of Experiment

The purpose of the present study was to optimize palbociclib loaded solid lipid nanoparticles (SLNs) by evaluating the relationship between design factors and experimental data. A three factor, three-level BoxBehnken design (BBD) was used for the optimization procedure, choosing the amount of tricapric, cremophor RH40 and soy lecithin, as independent variables. The chosen dependent variables were particlesize, entrapment efficiency and % cumulative drug released. The generated polynomial equations and response surface plots were used to relate the dependent and independent variables. The optimal nanoparticles were formulated with 08%tricapric, 09%cremophor RH40, and 6% soy lecithin. Three formulations were prepared according to these levels and found that the observed responses were close to the predicted values of the optimized formulation. The formulation PF13 was chosen for characterization as it displayed minimum particle size (103 nm), PI of 0.47, zeta potential of -16 mV, maximum drug release of 98% in 12h. The formulation was stable when stored according to ICH guidelines for 6 months. In vivo study results in rat plasma show that at any time, point, the drug plasma concentrations in animals administrated with optimised solid lipid nanoparticles was higher than that of pure drug. Cmax of the palbociclib optimised solid lipid nanoparticles 583.525±1.05 ng/ml was significant (p<0.05) as compared to the pure drug suspension formulation 110.45±1.64 ng/ml. Tmax of both optimised solid lipid nanoparticles formulation and pure drug was 2.0±0.03and 4.0±0.04 h, respectively. AUC0-∞ infinity for palbociclib optimised solid lipid nanoparticles formulation was higher (10159.1±1.85 ng.h/ml) than the pure drug suspension 2587.3±0.37 ng.h/ml.