This study investigates the effects of experimental conditions on the mechanical characterization of dissolving microneedles (MNs), which are novel transdermal drug delivery systems. The researchers used micromolding to fabricate PVA-based dissolving MN patches with eight different cone-shaped geometries. They found that compression speed and the number of compression needles significantly affected the needle fracture force. The needle fracture force was negatively correlated with the aspect ratio of the needles, and higher residual water or higher loading of lidocaine hydrochloride decreased the needle fracture force. The findings highlight the importance of setting appropriate methods and parameters for characterizing the mechanical properties of dissolving MNs to ensure their quality and safety. The study also suggests that dissolving MNs can be categorized into two groups based on their aspect ratio, with buckling and unbuckling deformation occurring at aspect ratios of 2.8 and 1.8, respectively. The results provide valuable insights for optimizing the design and quality control of dissolving MNs.This study investigates the effects of experimental conditions on the mechanical characterization of dissolving microneedles (MNs), which are novel transdermal drug delivery systems. The researchers used micromolding to fabricate PVA-based dissolving MN patches with eight different cone-shaped geometries. They found that compression speed and the number of compression needles significantly affected the needle fracture force. The needle fracture force was negatively correlated with the aspect ratio of the needles, and higher residual water or higher loading of lidocaine hydrochloride decreased the needle fracture force. The findings highlight the importance of setting appropriate methods and parameters for characterizing the mechanical properties of dissolving MNs to ensure their quality and safety. The study also suggests that dissolving MNs can be categorized into two groups based on their aspect ratio, with buckling and unbuckling deformation occurring at aspect ratios of 2.8 and 1.8, respectively. The results provide valuable insights for optimizing the design and quality control of dissolving MNs.