Formulation and physicochemical characterisation of fenofibrate-loaded lipid nanoparticles

Abstract

The aims of this thesis were to develop fenofibrate-loaded lipid nanoparticles (FLNs) in both dispersion and freeze-dried forms, and to study the effects of process parameters on theirs physicochemical properties and their stability. The formulations studied were composed of lipid excipients and surfactant mixtures. These lipid excipients were cetyl palmitate (CP) wax, medium-chain triglycerides (MCT) oil, and one of four glycerides either trimyristin (TM), hydrogenated palm oil (HPO), glyceryl behenate (GB) or glyceryl palmitostearate (GPS), while the surfactant mixture was made of polysorbate 80 and lecithin. The samples were prepared by hot high pressure homogenisation technique. The results revealed that an increase in the homogenised cycle and pressure brought a decrease in the particle size of FLNs. They were also affected by the types and amounts of the lipid and the surfactant concentrations. A formulation containing either GPS or GB diglycerides as co-lipid was found to be capable of generating particles in the 30 nm range. For the freeze-dried forms, the small particle sizes could be maintained by using hydrophilic surfactants which were not crystallised during the freeze-drying process, with high amount of cryoprotectant or without. DSC and X-ray diffraction studies on freeze-dried form revealed that the freeze-drying process had no impact on the polymorphic transformation of lipids. Most formulations showed β′ form while the formulation containing TM as co-lipid revealed the combination of stable β form and metastable β′ form. Although those formulations have some different in lipid modification, the high drug entrapment was achieved in dispersion and freeze-dried form but the former had a poor dissolution. However, the stability data demonstrated that FLNs and their freeze-dried products remained stable, both physical and chemical, over 3 months at 30 °C.