Precipitation of ultrafine particles using liquid antisolvent with concentric ultrasonic nozzle and subcritical CO2

Nanotechnology has become more relevant in the pharmaceutical industry. Almost 40% of the drugs developed by pharmaceutical industries are poorly soluble in water which limits the bioavailability of these drugs in body fluids. Hence, it is necessary to reduce the particle size, which increases the interfacial surface area. This work focuses on micronization of class ii drug Griseofulvin which is poorly water soluble. Two processes namely, liquid antisolvent precipitation using ultrasonic nozzle and other process using subcritical CO2 have been used to produce ultrafine particles of this drug. In liquid antisolvent precipitation, a combination of ultrasound, polymer and surfactant is used to precipitate ultrafine particles. Ultrasound is used to increase the nucleation rate by enhancing the micro mixing of solvent and antisolvent stream and decrease the agglomeration. Surfactants and polymers are used to reduce the surface tension and thereby increase the nucleation rate. Use of additives can inhibit the particle growth and reduce the agglomeration. Particles in the range of 10 - 2 µm have been precipitated in this process. The process using subcritical CO2 has also been used to increase the micro mixing and to increase the nucleation rate. The depressurization of CO2 expanded solutions of Griseofulvin, causes large temperature drop and hence induce low supersaturation an high nucleation rate. This results in precipitation of ultrafine particles. Particles in the range of 15 - 1 µm have been precipitated in this process