Effects of tablet crushing methods on solid-state properties, dissolution behavior, and dispensability of acetaminophen tablets

Purpose In clinical practice, tablets are often crushed and administered to patients with dysphagia or children, typically using a mortar and pestle, tablet crusher, or other methods of administration. Clinical tablet crushing may alter the physicochemical properties of drugs; however, the effects of crushing methods on pharmaceutical quality remain unclear. This study aimed to compare three crushing methods available to pharmacists, namely, a mortar and pestle, a tablet crusher, and an oscillatory ball mill (OBM), using the same acetaminophen (AA) tablets, and to relate the resulting solid-state properties to dissolution and to the loss of powder during automatic dividing and packaging, which determines the accuracy of the dispensed dose. Methods We evaluated the physicochemical properties of the crushed samples, including particle size distribution, SEM, PXRD, DSC, FTIR, dissolution, flowability, and dispensability. Results All crushing methods reduced the crystallinity, with OBM causing the greatest solid-state alteration. In contrast, the tablet crusher produced relatively fine particles and showed the most rapid initial dissolution under the experimental conditions. The weight loss during dividing and packaging was 1.0–3.3% with a V-shaped powder dispensing machine under all crushing conditions, whereas with a rotary disk-type machine, it reached 10.0% (tablet crusher, 5 min) and 8.5% (OBM, 5 min). Conclusion The crushing method and crushing time influenced the solid-state properties, dissolution, and packaging loss of AA tablets. No single method was superior in all respects; the method and crushing time should be selected according to the packaging machine used, and prolonged grinding with the OBM should be avoided.