Electrospray Crystallization for Nanosized Pharmaceuticals with Improved Properties

Abstract

Many new pharmaceuticals have low water solubility, hampering their pharmaceutical activity upon administering. One approach to increase solution concentrations during drug administration is to increase the surface-to-volume ratio by decreasing the crystal product size. Sub-micrometer-sized niflumic acid crystals were produced by electrospray crystallization. Electrospray crystallization uses a high potential difference to create a mist of ultrafine charged solution droplets. The subsequent total solvent evaporation and droplet disruption process lead to crystallization of sub-micrometer-sized crystals. For concentrations well below the solubility concentration while using small nozzle diameters, niflumic acid crystals with a size of 200-800 nm were produced. In the absence of excipients, for the sub-micrometer-sized niflumic acid no significantly different dissolution profile compared to the conventional one was measured. However, if excipients were added, the dissolution rate for the sub-micrometer-sized product increases substantially in stimulated gastric juice, while that of the conventional product increased slightly. Probably the excipients avoid the aggregation of the hydrophobic sub-micrometer particles in the low pH environment. © 2012 American Chemical Society.