Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ijpharm.2009.11.007
Title: A continuous and highly effective static mixing process for antisolvent precipitation of nanoparticles of poorly water-soluble drugs
Authors: Dong, Y.
Ng, W.K.
Hu, J.
Shen, S.
Tan, R.B.H. 
Keywords: Antisolvent precipitation
Dissolution rate
Oral bioavailability
Spironolactone
Static mixers
Issue Date: 15-Feb-2010
Source: Dong, Y., Ng, W.K., Hu, J., Shen, S., Tan, R.B.H. (2010-02-15). A continuous and highly effective static mixing process for antisolvent precipitation of nanoparticles of poorly water-soluble drugs. International Journal of Pharmaceutics 386 (1-2) : 256-261. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ijpharm.2009.11.007
Abstract: Rapid and homogeneous mixing of the solvent and antisolvent is critical to achieve submicron drug particles by antisolvent precipitation technique. This work aims to develop a continuous and highly effective static mixing process for antisolvent precipitation of nanoparticles of poorly water-soluble drugs with spironolactone as a model drug. Continuous antisolvent production of drug nanoparticles was carried out with a SMV DN25 static mixer comprising 6-18 mixing elements. The total flow rate ranged from 1.0 to 3.0 L/min while the flow rate ratio of solvent to antisolvent was maintained at 1:9. It is found that only 6 mixing elements were sufficient to precipitate the particles in the submicron range. Increasing the number of elements would further reduce the precipitated particle size. Increasing flow rate from 1.0 to 3.0 L/min did not further reduce the particle size, while higher drug concentrations led to particle size increase. XRD and SEM results demonstrated that the freshly precipitated drug nanoparticles are in the amorphous state, which would, in presence of the mixture of solvent and antisolvent, change to crystalline form in short time. The lyophilized spironolactone nanoparticles with lactose as lyoprotectant possessed good redispersibility and showed 6.6 and 3.3 times faster dissolution rate than that of lyophilized raw drug formulation in 5 and 10 min, respectively. The developed static mixing process exhibits high potential for continuous and large-scale antisolvent precipitation of submicron drug particles. © 2009 Elsevier B.V. All rights reserved.
Source Title: International Journal of Pharmaceutics
URI: http://scholarbank.nus.edu.sg/handle/10635/54029
ISSN: 03785173
DOI: 10.1016/j.ijpharm.2009.11.007
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