The aim of this article was to check the physical stability of the amorphous form of probucol at both standard storage and manufacturing conditions. Our studies clearly show that disordered form of the examined, cholesterol lowering, agent stored at ambient pressure does not reveal any tendency toward recrystallization. The physical stability of neat probucol stored at ambient pressure has been investigated (i) at room temperature by means of X-ray diffraction technique (XRD) as well as (ii) at T = 333 K by means of broadband dielectric spectroscopy (BDS). Due to the fact that compression is an important stage of drugs manufacturing we additionally performed physical stability tests of amorphous probucol at elevated pressure. The recrystallization tendency of the examined pharmaceutical has been tracked online from the initial and further up to a few hours after compression by means of the high pressure BDS technique. These experiments indicate that even very small pressure applied during the sample compression immediately induce its recrystallization. Since, the sensitivity on pressure eliminates probucol from the group of physically stable amorphous APIs, its stabilization is required. Taking into account that there are many scientific reports describing the positive effect of coadministration of probucol with the drug atorvastatin, we used the latter as probucol's crystallization inhibitor.
Keywords: BDS; atorvastatin; binary amorphous mixture; composition of probucol and atorvastatin; dielectric spectroscopy; molecular dynamic; online monitoring of the physical stability; probucol.