Enhanced Dissolution Rate of Dronedarone Hydrochloride via Preparation of Solid Dispersion using Vinylpyrrolidone‐Vinyl Acetate Copolymer (Kollidone® VA 64)

Abstract

Solid dispersion (SD) systems have been widely used to increase the dissolution rate and oral absorption of poorly water‐soluble compounds. In order to enhance the dissolution rate of dronedarone hydrochloride (DRN), a recent antiarrhythmic agent, SDs of DRN were formulated using conventional solvent evaporation method with amorphous polymers including hydroxypropyl methyl cellulose (HPMC), poly(vinyl pyrrolidone) (PVP), and vinylpyrrolidone‐vinyl acetate copolymer (VA64). The prepared SDs were characterized in terms of drug crystallinity, morphology, and in vitro dissolution profile in aqueous medium. The physical characterization using differential scanning calorimetry and X‐ray powder diffraction revealed that the active compound was molecularly dispersed in all polymeric carriers tested, in a stable amorphous form in drug to polymer ratios ranging from 1:0.5 to 1:2. The dissolution rates of DRN in all SDs were much higher than those from the corresponding physical mixture and drug powder alone. In particular, the greatest dissolution enhancement was obtained from the VA64‐based SD in a drug to polymer weight ratio of 1:1, achieving almost complete drug release after 120 min at pH 1.2. Thus, VA64‐based SD with higher drug dissolution rate along with a simple preparation process is suggested as an alternative for the oral formulation of the benzofuran derivative.