Understanding real-time water penetration dynamics in tablets using synchrotron X-ray micro-computed tomography

Understanding the initial water penetration dynamics in pharmaceutical tablets is critical-a precursor to drug bioavailability, yet the underlying mechanisms remain poorly understood. Using in-situ synchrotron X-ray-based micro-computed tomography (X-ray μCT), we visualized and quantified the microstructural changes in tablets composed of common excipients upon contact with a single water droplet. In pure microcrystalline cellulose (MCC PH-102 & PH-200), the hydrophobicity of the lubricant magnesium stearate (MgSt) was found to dictate water penetration, with 1% w/w MgSt significantly impeding penetration and promoting a more stable pore network compared to 0.25% w/w. Combining swelling MCC and rigid di-calcium phosphate (DCP) accelerated water penetration; here MCC-induced swelling generated synergistic pore expansion. Formulations containing the super disintegrant croscarmellose sodium (CCS) exhibited near instantaneous (