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 (<3 s) and rapid localized fragmentation, generating the highest porosity. Our findings reveal a complex interplay between excipient properties (swelling, rigidity, disruptive explosion), demonstrating that water penetration is governed by diverse and synergistic mechanisms. These crucial mechanistic insights are pivotal for the rational design of oral solid dosage forms with tailored formulations to improve oral bioavailability.