Preparation of naproxen–excipient formulations by CO2 precipitation on a slurry

Abstract

The work focused on screening the impact of various excipients and/or procedure in a new method that consists in a CO2-induced precipitation of a drug on a slurry. Naproxen (NPX) is a drug whose bioavailability could be improved by formulation with hydrophilic excipients. The investigated excipients were of various type, size and porosity, i.e. mannitol, silicas (SiO2 and SIO2 aminopropyl) and an anion exchange resin Duolite. The precipitation process used compressed CO2 as antisolvent for NPX and acetone as solvent to dissolve NPX and to suspend the excipient particles. Naproxen precipitated as crystals with a size distribution influenced by the NPX:excipient ratio for mannitol-based formulations. For other excipient co-precipitates, the overall size distributions were in the same range and below 330μm except for the 5μm silica. Due to the hydrophilic nature of the excipients, most formulations yielded an increased drug dissolution rate. Compared to physical mixtures, the benefit of the CO2 treatment was demonstrated in case of the excipient mannitol.