Preparation of Amorphous Probucol with Fluvastatin Sodium Salt and Stability Comparison Studies of Co-amorphous Probucol with Fluvastatin Sodium Salt and Atorvastatin Calcium Trihydrate Salt

A co-amorphous state composed of probucol (PC) and fluvastatin sodium salt (FLU) was prepared by spray-drying (SD). We have previously reported that PC and atorvastatin calcium trihydrate salt (ATO) formed a co-amorphous state when prepared by a SD method and that the solubility of PC and the amorphous stability were improved by the preparation of the co-amorphous state. In the present study, the physicochemical properties, including the amorphous stability of the prepared co-amorphous state, were characterized. Powder X-ray diffraction measurement results suggested that PC and FLU formed a co-amorphous state and that a higher percentage of PC was dissolved from the PC-FLU co-amorphous state than from the PC-ATO co-amorphous state. The results are attributed to FLU exhibiting greater solubility and wettability than ATO, which is supported by the results of solubility tests and contact-angle measurements. The stability of the amorphous state of PC is higher in the co-amorphous state with ATO than in that with FLU. This difference is attributed to differences in the molecular interaction modes between PC-FLU and PC-ATO. Therefore, the selection of high-wettability molecules as a co-former for the co-amorphous state enhances its water solubility. The present study also indicates that molecular interactions enhance the stability of the co- amorphous state.