Objective: The aim of this study was to enhance the solubility and dissolution rate of a poorly water-soluble antioxidant, hesperetin, by fabricating its nanoparticles using evaporative precipitation of nanosuspension (EPN) and antisolvent precipitation using syringe pump (APSP).
Methods: Hesperetin solution in ethanol at concentrations of 5, 10 and 15 mg/ml were prepared. For EPN, the solution was added to hexane (anti-solvent) and the nanosuspension formed was quickly evaporated to obtain the drug particles. For APSP, a syringe was filled with the prepared hesperetin solution, which was injected at a fixed flow rate (2 to 8 ml/min) into water (anti-solvent) under magnetic stirring (300 to 1000 rpm). Solvent to anti-solvent ratios used were 1:10, 1:15 and 1:25. The hesperetin particles were filtered and vacuum dried. The effect of temperature was also observed.
Results: The average particle size of the commercial drug was about 30 µm. The smallest average particle size obtained from EPN was around 460 nm and from APSP around 400 nm. Decreasing the drug concentration and temperature; and increasing the flow rate, stirring rate and solvent to anti-solvent ratio resulted in lower particle size. Differential scanning calorimetry and x-ray diffraction studies suggested that the crystallinity of hesperetin nanoparticles was reduced. The dissolution of hesperetin nanoparticles prepared was significantly higher than the commercial hesperetin.
Conclusions: This study demonstrated that both EPN and APSP can successfully prepare hesperetin nanoparticles which exhibit faster dissolution. However, drug nanoparticles prepared by APSP were more amorphous and hence, showed slightly better solubility and dissolution.