Solvent influence on manufacturability, phase behavior and morphology of amorphous solid dispersions prepared via bead coating

Abstract

Bead coating or fluid-bed coating serves as an auspicious solvent-based amorphous solid dispersion (ASD) manufacturing technique in respect of minimization of potential physical stability issues. However, the impact of solvent selection on the bead coating process and its resulting pellet formulation is, to the best of our knowledge, never investigated before. This study therefore aims to investigate the influence of the solvent on the bead coating process itself (i.e. manufacturability) and on solid-state characteristics of the resulting ASDs coated onto beads. For this purpose, the drug-polymer system felodipine (FEL)-poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) was coated onto microcrystalline cellulose (MCC) beads from acetonitrile (ACN), methanol (MeOH), ethanol (EtOH), acetone (Ac), 2-propanol (PrOH), dichloromethane (DCM) and ethyl acetate (EthAc). A drug loading screening approach with bead coating revealed analogous ability to manufacture high drug-loaded ASDs from the different organic solvents. The results show no correlation with crystallization tendency or with equilibrium solubility of the drug in the different solvents, nor with the solvent-dependent drug-polymer miscibility obtained from film casting experiments. Distinct coating morphologies were however observed for PVP-VA and FEL-PVP-VA ASDs deposited onto beads from the various solvents, which is attributed to differences in solvent evaporation kinetics.