Drug amorphisation by fluid bed hot-melt impregnation of mesoporous silica carriers

Abstract

• Solvent-free process for converting crystalline drug to amorphous form. • Successful co-fluidisation of ibuprofen and mesoporous silica particles. • No recrystallisation for drug loadings up to 50% wt. • Exceptional dissolution rate enhancement at both acidic and neutral pH. Amorphisation using mesoporous inorganic carriers represents an emerging formulation strategy for the dissolution rate enhancement of poorly water-soluble Active Pharmaceutical Ingredients (APIs). This approach employs API loading to a porous carrier, which stabilises the amorphous form and prevents recrystallisation due to spatial confinement in the mesopores. In this work, we utilise recently discovered silica particles with a unique pore structure that contain well-connected macropores for rapid capillary transport of the molten API, alongside mesopores for efficient drug amorphisation. We demonstrate that these particles enable efficient drug loading by a solvent-free process, namely hot-melt impregnation in a fluidised bed reactor. By controlling the process temperature and therefore the melt-in rate of the API, we show that the co-fluidisation of the API source crystals and silica carrier particles is possible without wall build-up or agglomeration. Using ibuprofen as a model API, we systematically investigate the effect of drug loading (30–50% w/w) and process conditions (heating time, process temperature) on the physico-chemical and dissolution properties of the product. The amorphous content of the silica particles after drug loading was established by DSC and XRPD and the chemical stability was confirmed by FTIR spectroscopy. More than a five-fold dissolution rate enhancement compared to crystalline API was achieved by fluid bed amorphisation.