Enhancing the oral bioavailability of poorly water-soluble amisupiride with solid nanodispersion

The limited oral bioavailability remains an essential challenge of poorly water-soluble amisupride (AMS). Herein, we designed a solid nanodispersion system of AMS (AMS-SN) by dispersing AMS into a polymeric matrix composed of Solutol HS-15, polyvinylpolypyrrolidone (PVPP), and poly (maleic anhydride-alt-1-octadecene) (PMHC18) to improve the oral bioavailability of AMS. AMS existed in the AMS-SN system in amorphous or molecular state. Moreover, AMS-SN could transform into nanometer-sized particles upon their exposure in the gastrointestinal fluids. Compared to the AMS suspension, the absorption of AMS in the duodenum, jejunum and ileum increased significantly by 8.02, 32.18 and 9.11-fold by the AMS-SN formulation, respectively. Particularly, the AMS-SN system produced an 8.58-fold enhancement of oral bioavailability of AMS. Therefore, solid nanodispersion provides a feasible pharmaceutical platform for oral delivery of poorly water-soluble drugs (PWSDs).

Automated summary

A solid nanodispersion system of poorly water-soluble amisupride (AMS) was designed by dispersing AMS into a polymeric matrix. The system exhibited a transformation into nanometer-sized particles upon exposure to gastrointestinal fluids and significantly improved the oral bioavailability of AMS. Compared to the AMS suspension, the absorption of AMS in different parts of the gastrointestinal tract increased significantly by 8.02, 32.18, and 9.11-fold, and the oral bioavailability of AMS was enhanced by 8.58-fold.