Silica particles with three levels of porosity for efficient melt amorphisation of drugs

Abstract Silica particles with a unique multi-level pore structure have been prepared in order to enable efficient melt-in amorphisation of pharmaceutical substances. The dissolution rate of drugs with a low aqueous solubility can be enhanced by their conversion from a crystalline to an amorphous form. In order to avoid spontaneous re-crystallisation over time, the amorphous form must be stabilised, in this case by melt-in sorption into a porous carrier. To stabilise the amorphous state, pore diameters not exceeding approximately ten times the equivalent molecular diameter are required. However, since the permeability of porous media scales with the square of the mean pore diameter, carrier particles with pores in the nanometer range suffer from slow melt-in rates. Therefore, silica particles with a novel multi-level porous structure have been proposed in this work. The particles combine a central hollow cavity, a network of conducting macro-pores for enhanced transport rate, and a mesoporous matrix for efficient stabilisation of the amorphous state. The particles were prepared by the hydrolysis of TEOS using a soft-templating method with octylamine. We show that by systematically modulating the hydrolysis rate by the presence of ethanol (a reaction by-product), particles with the desired pore structure, particle size and morphology can be formed. Furthermore, we demonstrate their superior transport properties during melt sorption, high drug loading capacity and the ability to stabilise the amorphous state of a drug.