International Journal of Pharmaceutics 456 (2013) 417–423 Contents lists available at ScienceDirect International Journal of Pharmaceutics j o ur nal ho me page: www.elsevier.com/locate/ijpharm Tailored beads made of dissolved cellulose—Investigation of their drug release properties Emrah Yildir a,∗ , Ruzica Kolakovic a , Natalja Genina a , Jani Trygg b , Martin Gericke b , Leena Hanski a , Henrik Ehlers a , Jukka Rantanen c , Mikko Tenho d , Pia Vuorela a , Pedro Fardim b , Niklas Sandler a a Pharmaceutical Sciences Laboratory, Department of Biosciences, Åbo Akademi University, Tykistökatu 6A, FI-20520 Turku, Finland b Laboratory of Fibre and Cellulose Technology, Department of Chemical Engineering, Åbo Akademi University, Porthansgatan 3, FI-20500 Turku, Finland c Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark d Laboratory of Industrial Physics, Department of Physics, University of Turku, FI-20014 Turku, Finland a r t i c l e i n f o Article history: Received 14 July 2013 Accepted 21 August 2013 Available online 4 September 2013 Keywords: Porous cellulose beads Drug delivery Macrospheres Drug loading Chemical imaging a b s t r a c t In the frame of this work, we have investigated drug entrapping and release abilities of new type of porous cellulose beads (CBs) as a spherical matrix system for drug delivery. For that purpose, CBs prepared with three different methods were used as drug carriers and three compounds, anhydrous theophylline (Thp), riboflavin 5 ′ -phosphate sodium (RSP) and lidocaine hydrochloride monohydrate (LiHCl) were used as model drug substances. The loading procedure was carried out by immersing swollen empty beads into the solutions of different concentrations of model drugs. The morphology of empty and loaded beads was examined using a field emission scanning electron microscopy (FE-SEM). Near-infrared (NIR) imaging was performed to identify the drug distributions on and within the loaded CBs. The drug amount incorporated into CBs was examined spectrophotometrically and in vitro drug release studies were performed to determine the drug release rates. The results of FE-SEM and chemical NIR imaging analyses revealed that incorporated drug were distributed on the surface and but also within the internal structure of the CBs. Physical properties of CBs and solubility of model drugs had effect on loading efficacy. Also, the drug release rates were controlled by solubility of model drugs (diffusion controlled release). In conclusion, CBs from dissolved cellulose show promise in achieving controlled drug delivery. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Cellulose beads (CBs), regenerated porous cellulose micro- spheres, can be prepared from cellulose solution of viscose (Peska et al., 1976a,b), cellulose fiber fragments (Davidson et al., 1993), microcrystalline cellulose (Newton et al., 1992) or regenerated cellulose (Loth and Fanter, 1993). The production of CBs was first reported in 1951 and several ways for their production have been developed over the years (O’neill and Reichardt, 1951). They became commercially available in 1970s (Peska et al., 1976a,b). So far CBs have found application in liquid chromatography, ion exchange processes, blood purification, separation and filtration of heavy metals, immobilization of enzymes (Ettanauer et al., 2011; Guo et al., 2007; ˇ Stamberg et al., 1982; Weber et al., 2005; Zhou et al., 2005). Over recent years, CBs have gotten a lot of attention ∗ Corresponding author at: Pharmaceutical Sciences Laboratory, Department of Biosciences, Biocity, Artillerigatan 6A, FI-20520 Turku, Finland. Tel.: +358 2 215 4837; fax: +358 44 9342698. E-mail address: eyildir@abo.fi (E. Yildir). in the pharmaceutical and biotechnological fields due to their biocompatibility, non-toxicity, high porosity, large specific surface area, mucoadhesivity, hydrophilic properties, chemical reactivity, high mechanical strength and relatively low cost (Thümmler et al., 2011; Volkert et al., 2009; Wolf, 1997; Wolf et al., 1996). In the literature, it has been described that the general procedure of making porous cellulose beads relies on the dispersing or drop- ping a solvent mixture of dissolved cellulose into a coagulating bath where cellulose beads are created by agglomeration/precipitation (Buschle-Diller et al., 1995; Ek et al., 1995; Sescousse et al., 2011; Tsao et al., 1978; Wolf et al., 1996). Many different methods have been developed by changing the solvent applied or changing the technique of dispersing/dropping the droplets for creating spher- ical CBs with diameters in the micro to millimeter scale (Chen and Tsao, 1976; Liebert et al., 2010; Luo and Zhang, 2010; Peska et al., 1976a,b; Pinnow et al., 2008). Most of these procedures use derivatizing solvents and include several disadvantages, such as using an excess of chemicals because of the de-derivatization step, using toxic CS 2 , which raises environmental issues. How- ever, the CBs, which have been used in this study were created by utilization of non-derivatizing and an environmental friendly 0378-5173/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ijpharm.2013.08.047