Optimization of Formulation and Operating Parameters for Ginkgo biloba Extract Nanosuspension by Wet Ball Milling Using a Box-Behnken Design

In the present work, the formulation of nanosuspension of Ginkgo biloba extract (GBE) and the operating parameters of wet ball milling (WBM) was optimized using the Box-Behnken design (BBD) method. The key formulation factors evaluated were GBE concentration, milling speed, milling time, and sodium dodecyl sulfate (SDS) concentration. A quadratic model with the correlation coefficient (R-2) value of 0.9276 was established based on the experimental data, implying that this model is significant; meanwhile, the analysis of variance (ANOVA) showed that the SDS concentration was the most significant factor on particle size, followed by GBE concentration, milling speed, and milling time was the slighter significant factor. The GBE nanosuspension with the particles size of 171.2 nm was prepared under the optimized conditions of GBE concentration (7.459 g/L) in combination with milling time (1.492 h), milling speed (9.253 m/s), and SDS concentration (0.846 g/L). The freeze-dried nanosuspension exhibited spherical particle morphology with uniform size by scanning electron microscopy. In addition, the melting behavior of the raw material and milled GBE was analyzed by differential scanning calorimetry and it was found that the melting point decreased due to the decrease of particle size. Furthermore, the dissolution rates of the optimized GBE showed better dissolution properties than the unprocessed GBE. The results show that it is feasible to prepare GBE nanosuspension on a commercial scale by WBM to increase the bioavailability of GBE.