Solidification of hesperidin nanosuspension by spray drying optimized by design of experiment (DoE).

Objective: To accelerate the determination of optimal spray drying parameters, a "Design of Experiment" (DoE) software was applied to produce well redispersible hesperidin nanocrystals.

Significance: For final solid dosage forms, aqueous liquid nanosuspensions need to be solidified, whereas spray drying is a large-scale cost-effective industrial process.

Methods: A nanosuspension with 18% (w/w) of hesperidin stabilized by 1% (w/w) of poloxamer 188 was produced by wet bead milling. The sizes of original and redispersed spray-dried nanosuspensions were determined by laser diffractometry (LD) and photon correlation spectroscopy (PCS) and used as effect parameters. In addition, light microscopy was performed to judge the redispersion quality.

Results: After a two-step design of MODDE 9, screening model and response surface model (RSM), the inlet temperature of spray dryer and the concentration of protectant (polyvinylpyrrolidone, PVP K25) were identified as the most important factors affecting the redispersion of nanocrystals. As predicted in the RSM modeling, when 5% (w/w) of PVP K25 was added in an 18% (w/w) of hesperidin nanosuspension, subsequently spray-dried at an inlet temperature of 100 °C, well redispersed solid nanocrystals with an average particle size of 276 nm were obtained. By the use of PVP K25, the saturation solubility of the redispersed nanocrystals in water was improved to 86.81 µg/ml, about 2.5-fold of the original nanosuspension. In addition, the dissolution velocity was accelerated.

Conclusions: This was attributed to the additional effects of steric stabilization on the nanocrystals and solubilization by the PVP polymer from spray drying.