From simplicity to complexity: how excipients shape stability and disintegration of immediate-release tablets

Physical stability is a critical aspect of tablet formulation, with excipients significantly influencing long-term tablet performance, especially under humid conditions. This study investigated storage-induced changes in increasingly complex tablet formulations by sequentially incorporating croscarmellose sodium (CCS), magnesium stearate (MgSt), and lactose into microcrystalline cellulose (MCC)-based tablets prepared at different porosities and stored at 50°C/75% RH for up to 42 days. Storage induced changes occurred through two distinct stages. The first stage was governed by moisture uptake, with most sorption occurring within the first day of storage, resulting in tablet swelling and tensile strength reductions of 16-51% depending on formulation and porosity. The rate of these structural changes was strongly correlated with sorption kinetics. The second stage occurred after moisture uptake had largely stabilised and was characterised by continued changes in liquid penetration and swelling behaviour (quantified by sessile drop analysis), and disintegration performance. These later changes were highly formulation dependent, with MgSt containing formulations showing the greatest deterioration, where disintegration times increased from approximately 40 s to 500 s after storage. DVS measurements successfully predicted moisture uptake and tensile strength evolution across formulations and porosity levels. The results demonstrate that tablet stability is governed by a sequence of moisture driven structural changes followed by slower performance related changes, providing a practical framework for predicting stability assessment and formulation development from short-term measurements.