Utilizing Drug Amorphous Solid Dispersions for the Preparation of Dronedarone per os Formulations

Abstract

Dronedarone (DRN), an antiarrhythmic drug, exhibits potent pharmacological effects in the management of cardiac arrhythmias. Despite its therapeutic potential, DRN faces formulation challenges due to its low aqueous solubility. Hence, the present study is dedicated to the examination of amorphous solid dispersions (ASDs) as a strategic approach for enhancing the solubility of DRN. Initially, the glass forming ability (GFA) of API was assessed alongside its thermal degradation profile, and it was revealed that DRN is a stable glass former (GFA III compound) that remains thermally stable up to approximately 200 °C. Subsequently, five commonly used ASD matrix/carriers, i.e., hydroxypropyl methylcellulose (HPMC), povidone (PVP), copovidone (PVP/VA), Soluplus® (SOL), and Eudragit® E PO (EPO), were screened for the formation of a DRN-based ASD using film casting and solvent shift methods, along with miscibility evaluation measurements. SOL proved to be the most promising matrix/carrier among the others, and, hence, was used to prepare DRN ASDs via the melt-quench method. The physicochemical characterization of the prepared systems (via pXRD) revealed the complete amorphization of the API within the matrix/carrier, while the system was physically stable for at least three months after its preparation. In vitro release studies for the ASDs, conducted under non-sink conditions, revealed the sustained supersaturation of the drug for at least 8 h. Finally, the use of attenuated total reflectance (ATR) FTIR spectroscopy showed the formation of a strong molecular interaction between the drug molecules and SOL.