Amorphous solid dispersions of triclabendazole: Keeping the supersaturated drug solution using poloxamers

Abstract

The dissolution performance of amorphous solid dispersions often leads to the formation of supersaturated drug solutions. However, in many cases, the drugs can recrystallize from those solutions and precipitate. Thus, this study evaluates whether two selected poloxamers, as carriers of amorphous solid dispersions, could avoid the recrystallization and further precipitation of the hydrophobic triclabendazole. Different systems were prepared by the melting method and then characterized in solid and liquid states. The findings indicated that the drug solubility increased more than twenty times, from 0.3 μg/mL (raw drug) to 3.53 μg/mL and 7.28 μg/mL in the presence of P188 and P237, respectively. A similar finding was observed for the drug dissolution, and P188 and P237 increased the drug dissolution to 90 and 100 %, respectively. This study also confirmed that P237 was more effective than P188 in avoiding drug precipitation. As seen by X-ray diffraction analysis, an almost complete amorphization of the drug was observed by increasing the ratio of the poloxamers. Thus, these findings help to understand the dissolution behavior and supersaturated state of triclabendazole from amorphous solid dispersions, which could be applied to other hydrophobic drugs.