Role of solid lipid nanoparticles as drug delivery vehicles on the pharmacokinetic variability of Erlotinib HCl

Abstract

Background and objectivesErlotinib HCl is approved for the treatment of metastatic non-small cell lung cancer. Owing to its poor aqueous solubility and presystemic metabolism, Erlotinib HCl has poor oral bioavailability. Presence of food shows the variability in pharmacokinetics of erlotinib especially in absorption. The present study is aimed at developing solid lipid nanoparticles for Erlotinib HCl and evaluate their role on the bioavailability and food dependent variability in its absorption. MethodsSolid lipid nano particles were formulated by rota evaporation melt method and characterized by zeta sizer, FT-IR spectroscopy, X-ray diffraction and differential scanning calorimetry and In vivo pharmacokinetic studies in SD rats. A sensitive and specific high-performance liquid chromatography method was developed for the determination drug concentration in rat's plasma. The pharmacokinetic data was analysed using phoenix 32 WinNonlin software. ResultsThe average particle size and zeta potential of the optimized Erlotinib SLN was found to be 177 nm and −33 mV. All the characterization studies indicated there were no interactions between drug and excipients and the drug is inside the nanoparticles. Linearity was observed for the Erlotinib HCl in rat's plasma from 5 to 30 μg/mL. In vivo pharmacokinetics study in rat model showed significant increase in the oral bioavailability (2.12-fold) and reduced variability in area under the curve (from 2.5 to 1.4) from fed to fasted state using solid lipid nanoparticles over the plain drug. ConclusionSolid lipid nanoparticles showed significant improvement in bioavailability along with reduction in pharmacokinetic variability.