Characterization of spray dried chitosan–TPP microparticles formed by two- and three-fluid nozzles Ondřej Kašpar, Martin Jakubec, František Štěpánek ⁎ Department of Chemical Engineering, Institute of Chemical Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic abstract article info Available online 10 July 2012 Keywords: Spray drying Encapsulation Biopolymer Swelling Zeta potential Core–shell particle Chitosan microparticles cross-linked by tri-polyphosphate (TPP) anions have been prepared by spray drying. Two different cross-linking methods have been employed — ex-situ cross-linking whereby aqueous solution of cross-linked chitosan nanoparticles has been spray-dried by a two-fluid nozzle, and a novel in-situ cross- linking method, whereby solutions of chitosan and TPP have been fed to a three-fluid nozzle and cross- linking occurred within individual droplets. The size and morphology of the resulting microparticles have been characterised and their dependence on the cross-linking ratio and the initial chitosan concentration de- termined. Particles produced by the three-fluid nozzle were found to have favourable properties in terms of stability in aqueous media and they allow the use of higher chitosan concentrations, which makes them suit- able for microencapsulation applications. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Spray drying is a widely used particle formation process by which aqueous or organic solutions, emulsions and suspensions can be converted into a dry powder with a relatively narrow particle size dis- tribution. Thanks to short contact times, spray drying is well suited even for heat-sensitive materials (enzymes, drugs) [1]. In addition, corrosive and abrasive materials can be readily accommodated be- cause the contact between the mechanical parts and the materials is minimal as compared with other particle formation processes such as granulation. The physical properties of the resulting product (such as particle size and shape, moisture content, and flow proper- ties) can be controlled through the selection of equipment (type of nozzle) and the manipulation of process variables (gas and liquid flow rates, atomising gas pressure or inlet temperature). A key step in spray drying is the atomization of the feed liquid into fine droplets. This can be achieved by a range of nozzle types — centrifugal nozzles for the processing of dense suspension, single-phase pressure nozzles or two-fluid kinetic nozzles for the spraying of low to medium viscos- ity liquids at both laboratory and industrial scale. Other nozzle types such as piezoelectric droplet generators have also been reported in the context of spray drying although their use tends to be mainly at the laboratory scale [2]. Relatively recently, three-fluid kinetic nozzles have also been employed for spray drying, especially for the encapsu- lation of immiscible liquids such as oils or aromas [3]. The advantage of spray-drying techniques for application to microencapsulation is that it is reproducible, rapid, and relatively easy to scale up. One of the most commonly used compounds for microencapsulation purposes is chitosan thanks to its availability and excellent properties, such as being nontoxic, bioadhesive, and biodegradable [4]. For these reasons, chitosan has been used for the development of drug delivery systems for conventional drugs, protein drugs and DNA [5,6]. Chitosan microparticles not only protect the drug molecules from degradation, but also improve their uptake and bioavailability [7]. Chitosan is a hydro- philic polysaccharide, obtained by the deacetylation of chitin, which is the second most-abundant polysaccharide on Earth next to cellulose. Chitin is a basic component of protective cuticles of crabs, shrimps, lob- sters and cell walls of some fungi. Chitin is a straight homopolymer com- posed of β-(1,4)-linked N-acetyl-glucosamine units whilst chitosan comprises of copolymers of D-glucosamine and N-acetyl-glucosamine [8]. Chitosan is a weak base with a pKa value of the glucosamine residue of about 6.2–7.0 and therefore is insoluble at neutral and alkaline pH values [9]. In acidic medium, the amino groups of the polymer are pro- tonated, resulting in a soluble, positively charged polysaccharide that has a high charge density (one charge for each glucosamine unit). Due to the availability of free amino groups in chitosan, it carries a pos- itive charge and thus reacts with many negatively charged anions [8]. This fact is used for the formation of chitosan microparticles cross-linked by di- valent and polyvalent anions. Spray dried microspheres made of pure chi- tosan cannot be kept suspended in aqueous media for a long time because of their swelling and dissolution [6]. Therefore, non cross-linked chitosan microspheres prepared by spray-drying technique are unsuitable for the purpose of controlled drug delivery systems [10]. Commonly used cross-linking agents (e.g. formaldehyde) are toxic and thus not allowed Powder Technology 240 (2013) 31–40 ⁎ Corresponding author. Tel.: +420 220 443 236. E-mail address: Frantisek.Stepanek@vscht.cz (F. Štěpánek). 0032-5910/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.powtec.2012.07.010 Contents lists available at SciVerse ScienceDirect Powder Technology journal homepage: www.elsevier.com/locate/powtec