Posted by This study aimed to develop stable amorphous inclusion complexes of flurbiprofen (FP, used as a model drug) with two different cyclodextrins (CDs). Specifically, three-component amorphous systems were developed by co-grinding crystalline FP/β-CD complexes with either α- or γ-CD. Among these, the FP/β-CD/γ-CD system exhibited superior physical stability under accelerated humid conditions, whereas rapid crystallization occurred in binary amorphous FP/β-CD system. Notably, even a small amount of γ-CD (β-CD:γ-CD = 1:0.1) was sufficient to inhibit the crystallization of FP/β-CD complex, while α-CD and polyvinylpyrrolidone (PVP) were less effective. This stabilizing effect is likely attributed to the inherently low crystallization tendency of γ-CD. Crystallization inhibition was also observed in in vitro dissolution studies, where the amorphous FP/β-CD/γ-CD maintained a supersaturated state for a prolonged period compared to the amorphous FP/β-CD complex. In vivo absorption studies in rats revealed that the amorphous FP/β-CD/γ-CD significantly enhanced the oral absorption of FP, with 2.4-fold and 2.1-fold increases in Cmax and AUC, respectively, compared to FP alone. Even a small amount of γ-CD was sufficient to influence the absorption kinetics of FP.
Hiroto Ito, Fumitoshi Hirayama, Daisuke Iohara (2025) Preparation and Evaluation of Stable Amorphous Flurbiprofen Complexes Using Two Different Cyclodextrins. Journal of Pharmaceutical Sciences 103922.
https://doi.org/10.1016/j.xphs.2025.103922