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Journal of Pharmaceutics
Volume 2014, Article ID 265754, 14 pages
Review Article

Combinative Particle Size Reduction Technologies for the Production of Drug Nanocrystals

1Institute of Pharmacy, Department of Pharmaceutics, Biopharmaceutics and NutriCosmetics, Freie Universität Berlin, Kelchstraße 31, 12169 Berlin, Germany
2Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Knollstraße, 67061 Ludwigshafen am Rhein, Germany

Received 31 January 2013; Accepted 7 May 2013; Published 6 January 2014

Academic Editor: Waquar Ahsan

Copyright © 2014 Jaime Salazar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Nanosizing is a suitable method to enhance the dissolution rate and therefore the bioavailability of poorly soluble drugs. The success of the particle size reduction processes depends on critical factors such as the employed technology, equipment, and drug physicochemical properties. High pressure homogenization and wet bead milling are standard comminution techniques that have been already employed to successfully formulate poorly soluble drugs and bring them to market. However, these techniques have limitations in their particle size reduction performance, such as long production times and the necessity of employing a micronized drug as the starting material. This review article discusses the development of combinative methods, such as the NANOEDGE, H 96, H 69, H 42, and CT technologies. These processes were developed to improve the particle size reduction effectiveness of the standard techniques. These novel technologies can combine bottom-up and/or top-down techniques in a two-step process. The combinative processes lead in general to improved particle size reduction effectiveness. Faster production of drug nanocrystals and smaller final mean particle sizes are among the main advantages. The combinative particle size reduction technologies are very useful formulation tools, and they will continue acquiring importance for the production of drug nanocrystals.