Application of Precipitation Methods for the Production of Water-insoluble Drug Nanocrystals: Production Techniques and Stability of Nanocrystals

Dengning      Xia; Yong      Gan; Fude      Cui

Abstract

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, supercritical anti-solvent.

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Current Pharmaceutical Design

Title:Application of Precipitation Methods for the Production of Water-insoluble Drug Nanocrystals: Production Techniques and Stability of Nanocrystals

Volume: 20 Issue: 3

Author(s): Dengning Xia, Yong Gan and Fude Cui

Affiliation:

Keywords: Water insoluble drug, nanocrystals, anti-solvent, precipitation, stability, crystal grow and nucleation, stabilizer, flash precipitation, supercritical anti-solvent.

Abstract: 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.

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Xia Dengning, Gan Yong and Cui Fude, Application of Precipitation Methods for the Production of Water-insoluble Drug Nanocrystals: Production Techniques and Stability of Nanocrystals, Current Pharmaceutical Design 2014; 20 (3) . https://dx.doi.org/10.2174/13816128113199990397

DOI https://dx.doi.org/10.2174/13816128113199990397	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286

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