Zingiber purpureum is a traditional medicine employed in the treatment of various ailments, including
digestive disorders (stomachache, diarrhea, flatulence), inflammation (muscle aches, sprains),
respiratory problems (coughs, asthma), and women's health issues (menstrual cramps, postpartum
recovery). Its therapeutic activities are attributed to its phenolic and flavonoid content. This study
aims to investigate the use of high-energy ball milling to enhance the bioavailability of Z. purpureum
rhizome extract by reducing particle size to a nanoscale. The optimization process of milling included
ball-to-powder ratio, milling time, and rotation speed. The physicochemical properties and biological
activities of the milled extract were characterized using various techniques, including the particle
morphology using electron microscope (SEM), particle size analysis (PSA), thermogravimetric analysis
(TGA), crystallinity using X-ray diffraction (XRD), chemical structure analysis using Fourier-transform
infrared spectroscopy (FTIR), solubilization rate testing, determination of total phenol and flavonoid
content, and DPPH radical scavenging assay. The optimal milling process was achieved in 30 minutes,
speed of 500 rpm, and a 15:1 ball-to-powder ratio, resulting in a significant reduction in particle size
from 4,856.3 nm to 456.6 nm. XRD analysis showed similar diffraction patterns from the extract
before and after milling, with a slight decrease in the crystallinity index from 18.6% to 10.1%. FTIR
analysis confirmed that the milling process did not alter the functional groups present in the extract
however a change in the intensity of the peak due to alteration of hydrogen bonds in the nano
extract. SEM imaging revealed changes in particle morphology, including a decrease in observable size
followed with agglomeration formation. The nano extract exhibited enhanced dissolution, as
evidenced by increased total phenol content (5.08 to 6.86 mg GAE/g) and total flavonoid content
(from 3.26 to 5.24 mg QE/g). This improved dissolution correlated with increased DPPH radical
scavenging activity (IC50 from 258.62 mg/mL to 107.43 mg/mL). Based on these findings, it is
concluded that high-energy ball milling successfully modifies the physicochemical properties and
enhances the biological activity of Zingiber purpureum rhizome extract.