Fabrication of fenofibrate nanocrystals by probe sonication method for enhancement of dissolution rate and oral bioavailability

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2013-08, Vol.108, p.366-373
• Main Authors: Ige, Pradum Pundlikrao, Baria, Rohan K., Gattani, Surendra G.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Area Under Curve; bioavailability; Biological Availability; colloids; Drug Stability; drugs; Female; Fenofibrate; Fenofibrate - chemistry; Fenofibrate - pharmacokinetics; Fourier transform infrared spectroscopy; Freeze Drying; hypercholesterolemia; hypertriglyceridemia; Hypolipidemic Agents - chemistry; Hypolipidemic Agents - pharmacokinetics; Long term stability studies; Lyophilization; Male; Microscopy, Electron, Scanning; nanocrystals; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Oral bioavailability; Particle Size; pharmacokinetics; Polydispersity index; Powders; Rabbits; scanning electron microscopy; Similarity factor; Sodium Dodecyl Sulfate; Solubility; Sonication; Spectroscopy, Fourier Transform Infrared; zeta potential
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2013.02.043

Photographic image of pure fenofibrate (FBT) and different lyophilized batches of nanocrystals (FNS1, FNS2 and FNS3). •We used the probe sonicator for fenofibrate nanocrystals preparation.•We stabilized the nanosuspension using optimum concentration of poloxamer 188.•Fenofibrate nanocrystals showed improved solubility and oral bioavailability. Fenofibrate (FBT) is lipophillic drug used in hypercholesterolemia and hypertriglyceridemia having logP 5.375, low solubility (practically insoluble in water) and low oral bioavailability (36%). The purpose of work was to develop FBT nanocrystals for the enhancement of solubility and oral bioavailability. Fenofibrate nanosuspension was prepared using probe sonicator and transformed into dry powder using freeze drying and characterized by DSC, FTIR, XRPD, SEM, particle size, polydispersity index (PDI), zeta potential, solubility, in vitro dissolution, in vivo bioavailability and stability studies. Formulation FNS3 and pure drug exhibited the in vitro dissolution about 73.89% and 8.53% in 1% sodium lauryl sulfate (SLS) media, respectively. When the particle size reduced from 80,000±923nm to 460±20nm, saturation solubility was significantly increased. The saturation solubility of formulation FNS3 in 0.5% and 1% of SLS media found to be 67.51±1.5μg/mL and 107±1.9μg/mL, respectively. While, the saturation solubility of pure drug in 0.5% and 1% of SLS was found to be 6.02±1.51μg/ml and 23.54±1.54μg/ml, respectively. The pharmacokinetic study of optimized nanocrystals (FNS3) conducted in New Zealand white rabbits showed 4.73-fold increase in relative bioavailability than that of pure drug. Long term stability studies showed that there was no significant change in the mean particle size and PDI at 5°C±3°C after 180 days. This enhanced dissolution and bioavailability of fenofibrate nanocrystals could be the promising approach for oral delivery.