Preparation and Bioavailability Evaluation of Fenofibrate Nanosuspension
|Keywords||fenofibrate nanoparticles nanosuspension bioavailability|
The poor solubility of drug is the major obstacle in enhancing drug pharmacological and new drug development. It has been estimated that 50%of drugs in development have poor bioavailability due to low aqueous solubility and thus leads to significant side effects of drugs, limiting valuable chemical entity in clinical application.The using of new formulation technologies such as emulsification, solubilization, microemulsions etc will solve a certain extent problems caused by the poor solubility drugs which discussed before. However, these techniques will lose its effects when pharmaceutical products encountered body fluids and diluted. Thus, there is no fundamental solution for the problems of insoluble drugs absorption. Nanocrystals technology appeared on the end of century shows promise for poor soluble drugs. So far, there have been serveral of the nanocrystallization oral formulation of insoluble drug marketed in overseas and these new formulations have better and inerratic absorption, bioavailability show a certain extent increasing and can eliminate the food effect to the drug absorption.This topic was using aqueous solvent diffusion to prepare the nanoparticles of fenofribate which is an insoluble drug, study the composition of nanoparticles, solvent of drug, aqueous dispersion medium fomulation and the preparation conditions on particle size and stability of nanoparticles. Freeze-drying and spray-drying were used to pulverize the nanoparticles of drugs, respectively, explore the composition of drying protective agent and the preparation to the re-disperse of nanoparticles and its stability. Nanoparticles powder were capsulated as fenofribate nanosuspension capsule, observe it in vitro dissolution characteristics. Fasted and fed rats were intragastrical administrate nanosuspension, respectively, studying the in vivo absorption and comparing commercially micronized fenofribate capsules, evaluated the relative bioavailability.The reults showed that using solvent diffusion method with 0.05%chitosan and 0.2%polyvinyl (PVA) as aqueous phase, fenofribate nanoparticles were quickly produced, the average size of nanoparticle will be 333.9±50.2nm, zeta potential 24.2±1.2mV. The nanosuspension system was kept 5 hours at room temperature and the average size of particles have no significant change, consistent with the requirements of the production of post-processing. Polyvinylpyrrolidone (PVP), poloxamer 188 and mannitol were used as protective agent in spray-drying to prepare the powder of drug nanoparticles, the podwer of nanoparticles can be hydrated quickly and the average size of nanoparticles was 272.2±43.1 nm. Re-dispersed nanoparticles can maintain in nanometer scale within 1 hour in vitro, which meet the requirements of absorption in the body. Nanosuspension of fenofribate capsules in vitro dissolution rate was a bite slower than than the commercially micronized capsules (Lipanthyl), but its accumulated dissolution can still reach to 60%above within 45 minutes. Under fed and fasted conditions, the relative bioavailability has reached to 136.45%and 148.48%compared with the commercially capsule.