Investigation of Variables Related to the Formulation of Apixaban Nanostructured Lipid Carriers

Abstract

The objective of this research was to investigate and optimize the potential of nanostructured lipid carriers (NLCs) as a carrier system for Apixaban, which is an inhibitor of coagulation factor Xa have poor solubility and low bioavailability (F=50). Nanostructured lipid carriers (NLC) of apixaban were prepared by the ultra-sonication method with the aim of improving the pharmacokinetic behavior of apixaban and to increase patient compliance. Ten formulas of NLCs were prepared using glyceryl monostearate as solid lipid, and oleic acid as liquid lipid at different ratios in addition to different surfactants include Tween 80, Tween 20, or Poloxamer188 at different ratios. The prepared formulas were characterized regarding drug content, particle size analysis, polydispersity, entrapment efficiency, Zeta-potential, FT-IR, DSC, and in vitro dissolution study. All NLC had shown entrapment efficiency within a range of 64.53 to 89.02%. All prepared NLC has a particle size in nanometer but only four formulas particle size lower than 100nm. Both entrapment efficiency and release rate were affected by lipid concentration. Formula F6 which composed of Glyceryl mono-stearate 56.83%, Oleic acid 16.5%, Tween (80) 8.88%, and water up to 100%w/w was considered as a selected formula depending on its smallest particle size (42.1nm) and good physical properties in addition to promising release profile. The optimized formulation did not show remarkable physicochemical changes during preparation according to FT-IR and DSC results. It was concluded that the formulated NLC has a potential approach for controlled release of drug which may reduce the dose frequency and improves patient compliance.