This review focuses on using precipitation (bottom-up) method to produce water-insoluble drug nanocrystals, and the stability
issues of nanocrystals. The precipitation techniques for production of ultra-fine particles have been widely researched for last few decades.
In these techniques, precipitation of solute is achieved by addition of a non-solvent for solute called anti-solvent to decrease the
solvent power for the solute dissolved in a solution. The anti-solvent can be water, organic solvents or supercritical fluids. In this paper,
efforts have been made to review the precipitation techniques involving the anti-solvent precipitation by simple mixing, impinging jet
mixing, multi-inlet vortex mixing, the using of high-gravity, ultrasonic waves and supercritical fluids. The key to the success of yielding
stable nanocrystals in these techniques is to control the nucleation kinetics and particle growth through mixing during precipitation based
on crystallization theories. The stability issues of the nanocrystals, such as sedimentation, Ostwald ripening, agglomeration and cementing
of crystals, change of crystalline state, and the approaches to stabilizing nanocrystals are also discussed in detail.
Keywords: Water insoluble drug, nanocrystals, anti-solvent, precipitation, stability, crystal grow and nucleation, stabilizer, flash precipitation,
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