Chemical Engineering and Processing 71 (2013) 51–58 Contents lists available at ScienceDirect Chemical Engineering and Processing: Process Intensification jo ur nal homepage: www.elsevier.com/locate/cep Nanoparticle generation by intensified solution crystallization using cold plasma N. Radacsi a , A.E.D.M. van der Heijden a,b , A.I. Stankiewicz a , J.H. ter Horst a,∗ a Process & Energy Department, Delft University of Technology, Delft 2628 CA, The Netherlands b Technical Sciences, TNO, Rijswijk 2280 AA, The Netherlands a r t i c l e i n f o Article history: Received 7 December 2012 Received in revised form 27 February 2013 Accepted 1 March 2013 Available online 14 March 2013 Keywords: Nanoparticle synthesis Cold plasma Process intensification RDX API Niflumic acid Crystallization a b s t r a c t In this study, atmospheric pressure cold plasma (surface dielectric barrier discharge) was used as an alternative energy form to intensify solution crystallization and produce nano-sized organic crystals. Nano-sized particles can have beneficial product properties such as improved internal quality and dissolu- tion rate, compared to conventionally sized crystalline products. In cold plasma intensified crystallization a nebulizer system sprays the solution aerosol into the plasma with the help of a carrier gas. The plasma simultaneously heats and charges the droplets causing fast solvent evaporation and Coulomb-fission to occur, after which nucleation and crystal growth commence within the small, confined volume offered by the small droplets. In this manner, nano-sized crystals of the energetic material RDX and the pharma- ceutical niflumic acid were produced. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Crystallization is one of the most important separation and product technologies in the chemical and pharmaceutical indus- tries. Over the last decade, there has been increased interest in the application of alternative energy forms in crystallization [1–3]. The advantages of intensified crystallization processes consist of intensified process control, and/or improved product quality. For instance, by using electric fields, it is possible to produce nano- sized crystals [3], which can have strikingly different chemical and physical properties than conventionally sized crystals due to the increased importance of surface properties. Since smaller particles have a much higher specific surface area, an increase in the overall dissolution rate (the total amount of drug substance that dissolves per unit time) is expected at the same driving force for dissolution. Nano-sized crystals are furthermore too small to contain inclusions of which the size is usually in the micron size range. These inclu- sions of pockets of mother liquor generally cause other crystalline defects, like dislocations [4]. Therefore, the internal quality of nano- sized crystals is considered to be higher than the conventional, micron-sized (100–400 m) crystals [3]. Spray drying is a crystallization method, which combines spray- ing (e.g. with the help of a nozzle) with drying by hot vapor ∗ Corresponding author. E-mail address: J.H.terHorst@tudelft.nl (J.H. ter Horst). [5]. Spray drying is an inexpensive technique for the production of submicron-sized particles with relatively high yields (70–90%) [6]. Another inexpensive spraying method is electrospray crystal- lization, which is capable of producing crystals in the nano-size range by using an electric field as an alternative energy source. The key is to electrically charge solution droplets above a cer- tain threshold (Rayleigh-limit), where the electrostatic repulsion can overcome the surface tension, leading to the disruption of the droplets into much smaller droplets (Coulomb-fission) [7,8]. Due to the solvent evaporation, eventually supersaturation is achieved and crystallization of submicron particles can commence. Electrospray crystallization is an efficient and simple method for the production of nano-sized crystals, but it suffers from a low production rate and it is challenging to scale up since a narrow nozzle has to be used in combination with a low flow rate. Cold plasma crystallization combines the advantages of spray drying and electrospray crys- tallization, namely by enhancing the evaporation of the solution droplets by heating and producing submicrometer-sized crystals by electrically charging the solution droplets to induce Coulomb- fission. Plasma has several application areas from electronics to thermal coatings, treatment of polymers, fuel conversion and hydrogen production [9], surface treatment [10], disinfection [11], etc. However, the applicability of plasmas for solution crystalliza- tion has not been investigated so far due to the harsh plasma environment. The main goal of process intensification (PI) is to make sub- stantial improvements to the efficiency of chemical processes 0255-2701/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.cep.2013.03.002