LAUSR

ABSTRACT Saccharides have been applied as a water‐soluble matrix for dispersing hydrophobic drugs homogeneously without the need to use surfactants in amorphous solid dispersions (ASD). Up to now, concomitant permeability improvement of BCS Class IV drug by such matrices have not been much appreciated. Herein, an amorphous chitosan oligosaccharide (COS) was used as matrix to prepare surfactant‐free ASD of BCS class IV drug by the ball milling method, with curcumin (CUR) as a model drug. The DSC, XRPD, FTIR and physical stability experiments indicated that CUR was in an amorphous state with high physical stability and exhibited potential interactions with COS in the ASD. Non‐sink dissolution in vitro studies showed the maximum dissolution concentration of all CUR‐COS ASD (CUR and COS at weight ratios of 1:1, 1:2 and 1:4) reached ranging from 97.85 to 101.21&mgr;g/mL, far above that of pure CUR. The supersaturated concentration remained for at least 24h under non‐sink condition. Caco‐2 cell model revealed that, compared to the pure CUR group, the apparent permeability coefficients were increased by 1.72–4.44‐fold in all three CUR‐COS ASD, which was mainly attributed to opening the tight junctions of Caco‐2 cells by COS. The pharmacokinetic study showed that all CUR‐COS ASD groups exhibited significant enhancements in AUC0‐∞, with 1.55–3.01‐fold that of pure CUR (p<0.01). Tmax of CUR was shortened after oral administration of all three ASD. The current study demonstrates the amorphous COS could be used as a promising matrix in ASD for enhancing the oral bioavailability of BCS class IV drug by improving dissolution behavior and membrane permeability.