Analysis of submicron-sized niflumic acid crystals prepared by electrospray crystallization

Schematic of the electrospray crystallization process. Using a small nozzle diameter (d), a low constant flow rate (φ), relatively low solute concentration (c) a jet of highly charged small droplets will be emitted from the cone appearing at the nozzle tip when applying a high enough potential difference (ΔU) at a certain working distance (D). [Display omitted] ► Electrospray crystallization as a non-conventional method was used to formulate submicron-sized nifluminic acid crystals with a mean size of around 500nm. ► Electrosprayed product was partly amorphous right after the production, and only 81% of the sample was crystalline. ► Nifluminic acid crystals were chemically stable before and after the procedure. Interest in submicron-sized drug particles has emerged from both laboratory and industrial perspectives in the last decade. Production of crystals in the nano size scale offers a novel way to particles for drug formulation solving formulation problems of drugs with low solubility in class II of the Biopharmaceutical Classification System. In this work niflumic acid nanoparticles with a size range of 200–800nm were produced by the novel crystallization method, electrospray crystallization. Their properties were compared to those from evaporative and anti-solvent crystallizations, using the same organic solvent, acetone. There is a remarkable difference in the product crystal size depending on the applied methods. The size and morphology were analyzed by scanning electron microscopy and laser diffraction. The structure of the samples was investigated using differential scanning calorimetry, Fourier-transformed infrared spectroscopy and X-ray powder diffraction. The particles produced using electrospray crystallization process were probably changing from amorphous to crystalline state after the procedure.