Amorphous solid dispersions enhance the dissolution and oral bioavailability of poorly water-soluble drugs. However, the link between polymer properties and formulation performance has not been fully clarified yet. We studied the effect of hydroxypropyl cellulose (HPC) polymers molecular weight (Mw) on the storage stability, dissolution kinetics and supersaturation stability of spray-dried amorphous glibenclamide (GLB) formulations. The solid-state stability of amorphous GLB during storage was significantly enhanced by both the 40 kDa (HPC-SSL) and 84 kDa (HPC-L) polymers, regardless of Mw differences. In contrast, HPC-SSL maintained significantly higher aqueous drug concentrations during dissolution, compared to HPC-L (its higher Mw analogue). Dedicated dissolution experiments, in situ optical microscopy and solid-state characterization revealed that aqueous drug concentrations were determined by the interplay between crystallization inhibition, drug ionization, wetting and solubilization effects: (1) HPC prevents surface nucleation, hence inhibiting crystallization, (2) intestinal colloids (bile salts and phospholipids) increase supersaturated drug concentrations via wetting and solubilization effects and (3) pH and drug ionization severely impact the degree of supersaturation. The better performance of the lower Mw HPC-SSL was due to its superior inhibition of surface crystallization during dissolution. These insights into the molecular mechanisms of dissolution and crystallization of amorphous solids provide foundation for rational formulation development.

High plasma concentrations of cholesterol are associated with cardio-vascular disease complications and high risk of myocardial infarction. The absorption of dietary cholesterol depends on its bioaccessibility, which is in turn influenced by phytosterols, saponins and lipid digestion products. Therefore, we explored the interplay between phytosterols, Quillaja Dry saponin extract (QD), their combinations and lipid digestion on cholesterol bioaccessibility via an in vitro.