Application of curcumin as a co-former and an efflux inhibitor in paclitaxel co-amorphous mixture

The co-amorphous (CAM) system has attracted widely attention for improving the solubility of poor water solubility drug and provide a formulation strategy for combination administration system. Paclitaxel (PTX) belongs to biopharmaceutics classification system (BCS) class Ⅳ drug, with the poor water solubility and membrane permeability. This study aimed to preparing the CAM system between PTX and curcumin (CUR) by rotary evaporation method. The solid-state characterization of CAM indicated that the PTX and CUR presented as amorphous state, compared with crystalline PTX and CUR, the amorphous system could improve the saturated solubility and dissolution with significantly difference, besides, the PTX absorption permeability increased after amorphization with CUR, and the rat pharmacokinetic study exhibited that the PTX-CUR had a high Cmax and AUC0-∞ compared with crystalline CUR and PTX, Furthermore, the amorphous CUR and PTX exhibited the stronger anti-tumor efficacy in A549 cell model in vivo. In addition, PTX-CUR exhibited physical stability under the long-term storage condition. In conclusion, amorphization of PTX and CUR provided a promising mothed to improve the anti-tumor efficacy and oral bioavailability of PTX.