Solvent-free direct formulation of poorly-soluble drugs to amorphous solid dispersion via melt-absorption

Abstract

To improve the dissolution properties of poorly water soluble active pharmaceutical ingredients (APIs), a solvent-free melt-absorption process was applied to directly load the APIs into mesoporous SBA-15 silica powder as an amorphous solid dispersion. Two model compounds, poorly aqueous soluble ibuprofen (IBU) and fenofibrate (FEN), were individually mixed with SBA-15 powder and heated above their respective melting points. Upon cooling, the physicochemical and solid-state properties of the solid dispersions were investigated by N2 adsorption, DSC, XRD, SEM and solid-state NMR. The molten API was found to be absorbed into the pores, confined within the nano-channels of SBA-15, and re-solidified to an amorphous solid dispersion. Due to the amorphous properties, the APIs showed a significant enhancement in dissolution rate as compared with the untreated crystalline APIs. Although the amorphous forms were not at thermodynamic equilibrium, the APIs exhibited excellent solid-state physical stability even under accelerated stress conditions. In comparison with APIs loaded using a co-spray drying process (previous work), the melt-absorption process required no organic solvent, produced powders with a coarser size distribution and more desirable flow properties. This solvent-free direct melt-absorption process can be used to formulate a wide range of poorly soluble drugs to be amorphous solid dispersions.