How Does the Addition of Kollidon^®VA64 Inhibit the Recrystallization and Improve Ezetimibe Dissolution from Amorphous Solid Dispersions?

Abstract

Amorphization serves as a strategy for the improvement of poor dissolution characteristics of many drug compounds. However, in many formulations the content of polymeric stabilizer is high, which is undesirable from the perspective of future applications. Thus, studying the composition-dependent stability of amorphous solid dispersions seems to be demanded. In this paper, we describe the amorphization of ezetimibe, a lipid-lowering drug, in the spray drying process and investigate the effect of polyvinylpyrrolidone-co-poly(vinyl acetate) (PVP/VA) content on the physical stability and dissolution characteristics of the drug. Fully amorphous systems were obtained when the concentration of the polymer in solid dispersion was as low as 20%. The amorphization led to the dissolution enhancement by even 70%, with a noticeable sudden increase at around 40% of PVP/VA content and very small variations for systems having 66–90% PVP/VA. It was also correlated to wettability characteristics of solid dispersions, which may suggest that in the vicinity of 40% of the polymer content, the behavior of the system becomes independent of the PVP/VA content.

Keywords

• ezetimibe
• solid dispersion
• amorphization
• dissolution
• contact angle