Improved Dissolution Properties of Co-amorphous Probucol with Atorvastatin Calcium Trihydrate Prepared by...

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Probucol (PC) exhibits low water solubility, limiting its therapeutic efficacy.
• Atorvastatin calcium trihydrate salt (ATO) serves as a co-former to enhance drug properties.
• Spray-drying is a common technique for amorphous solid dispersion formulation.

Purpose of the Study:

• To prepare a co-amorphous system of probucol (PC) and atorvastatin (ATO) using spray-drying.
• To characterize the physicochemical properties and stability of the co-amorphous system.
• To evaluate the impact of co-amorphization on the dissolution rate of probucol.

Main Methods:

• Spray-drying (SD) was employed to prepare the co-amorphous system of PC and ATO.
• Physicochemical characterization included powder X-ray diffraction (PXRD), thermal analysis, and FTIR.
• Dissolution tests and stability studies under accelerated conditions (40°C/75% RH) were performed.

Main Results:

• PXRD and thermal analysis confirmed the formation of a PC-ATO co-amorphous system via SD.
• The co-amorphous system exhibited enhanced dissolution profiles for PC compared to crystalline PC or physical mixtures.
• The co-amorphous material demonstrated superior stability, remaining amorphous for 35 days, unlike amorphous PC which crystallized within a day.

Conclusions:

• Spray-drying successfully produced a stable co-amorphous system of probucol and atorvastatin.
• Co-amorphization significantly improved the aqueous solubility and dissolution rate of probucol.
• This approach offers a viable strategy for enhancing the bioavailability of poorly soluble drugs like probucol.