Particle design of indomethacin using a four-fluid-nozzle spray-drying technique

The spray-drying technique has previously been utilized as a method of improving the solubility of solid dispersion for poorly water-soluble drugs. This method disperses the drug in a molecular-state carrier, forming an amorphous, high-energy condition. In this study, we prepare matrix particles using hydroxypropylmethylcellulose (HPMC), which comprises indomethacin (IM) (a water-insoluble drug) and a carrier, using a four-fluid-nozzle spray-dryer. For comparison, we also evaluate the results gained with a conventional two-fluid-nozzle spray-dryer. Observation of the particle morphology by a scanning electron microscopy (SEM) reveals that the particles from the spray-drying technique atomize to several microns and that they become spherical. Assessment of the crystallinity of the spray-dried samples by powder X-ray diffraction and differential scanning calorimetry demonstrates that the IM becomes amorphized. These results indicate that the system forms a solid dispersion and that the particles become matrix particles. In the IM-HPMC system, the four-fluid-nozzle spray-dried preparation with a mixing ratio of 1:1 indicates remarkably improved dissolution rates in all pH solutions tested.