Impact of disintegrants on the structure and disintegration of hydroxypropyl methylcellulose-based amorphous solid...

Amorphous solid dispersion (ASD) is a widely adopted strategy to enhance the solubility of poorly water-soluble drugs. However, disintegration delay after storage poses a significant challenge to formulation performance. This study investigates the influence of disintegrant characteristics on disintegration behavior of hydroxypropyl methylcellulose (HPMC)-based ASD tablets containing griseofulvin (GRF). Two disintegrants, croscarmellose sodium (CCS) and crospovidone (CPV), were evaluated for their effects on the physical structure and disintegration performance of HPMC-based ASDs tablets under accelerated storage conditions (40°C/75% relative humidity). Dynamic viscoelastic measurements, hardness testing and disintegration testing revealed that disintegrant type markedly affected HPMC structural reorganization after storage. Tablets with CCS exhibited plasticization and a temporary loosening of the structure initially. Over time, water retention by CCS facilitated the rearrangement of HPMC chains, leading to prolonged disintegration times. Conversely, CPV maintained a loose network structure due to its high wicking ability, which prevented significant structural changes and preserved the disintegration performance. Tablets without disintegrants showed significant disintegration delay, highlighting the critical role of disintegrant selection in ensuring effective drug absorption through rapid disintegration. These findings underscore the importance of understanding the disintegrant mechanisms for optimizing ASD formulations for improved bioavailability.