Stability studies of As 4 S 4 nanosuspension prepared by wet milling in Poloxamer 407 Zdenka Buj  náková *, Erika Dutková, Matej Baláž, Erika Turianicová, Peter Baláž Institute of Geotechnics, Slovak Academy of Sciences, Watsonova 45, Košice 040 01, Slovakia A R T I C L E I N F O Article history: Received 15 September 2014 Received in revised form 14 November 2014 Accepted 17 November 2014 Available online 18 November 2014 Keywords: Nanosuspension Stability Nanomilling Arsenic sulfide Particle size A B S T R A C T In this paper the stability of the arsenic sulfide (As 4 S 4 ) nanosuspension prepared by wet milling in a circulation mill in the environment of copolymer Poloxamer 407 was studied. The obtained As 4 S 4 particles in nanosuspension were of 100 nm in size. The influence of temperature and UV irradiation on the changes in physical and/or chemical properties was followed. Long-term stability was observed via particle size distribution and zeta potential measurements. Influence of UV irradiation was studied via UV–vis spectroscopy (UV–vis), photoluminicsence (PL) technique and Fourier transform infrared spectroscopy (FTIR) measurements. The best stability of the nanosuspension (24 weeks) was achieved when stored at 4  C and in the dark. ã 2014 Elsevier B.V. All rights reserved. 1. Introduction The preparation of hydrophobic drugs in the form of nano- suspensions represents a challenging and potentially useful method for improving their bioavailability. Nanosuspensions are defined as liquid sub-micron colloidal dispersions of nanosized drug particles that are stabilized by a suitable polymer and/or surfactant (Rabinov, 2004). Several technologies have been developed for preparation of nanosuspensions (e.g., milling, high-pressure homogenization, impinging jet, electro-spraying, liquid-based methods and supercritical fluid processes) (Wang et al., 2013). Among these, wet media milling is considered an attractive approach that permits relatively easy scale-up with respect to industrial pharmaceutical nanosuspension production (Merisko-Liversidge and Liversidge, 2011). During the milling process, the drug crystals break into smaller particles, and thus fresh surfaces are continuously generated (Baláž, 2008). In nanosuspensions, water-insoluble drugs become more soluble because of increasing the saturation solubility and the surface area available for dissolution. On the other hand, a nanosuspension is a thermodynamically unstable colloid disper- sion system. A high surface area associated with the small size of the particles results in high interfacial tension, which in turn results in an increase in the free energy of the system. The high surface energy of nano-sized crystals results in particle size growth, a phenomenon known as Ostwald ripening (Boistelle and Astier, 1988). During this process, coarse particles grow at the expense of the redissolution of fine particles (Kim, 2004), which are more soluble than large ones and mass transfer occurs from the fine to coarse particles (Liu et al., 2011). To hinder this phenomenon and consequently aggregation, the electrostatic or steric stabilizers are needed. Arsenic sulfide compounds have a long history of application in a traditional medicine (Wang, 2001). In recent years, they have been studied as promising drugs in cancer treatment (Wu and Ho, 2006; Ye et al., 2006; Baláž et al., 2009, 2012; Baláž and Sedlák, 2010; Wu et al., 2011; Yuan et al., 2013; Tian et al., 2014; Pastorek et al., 2014). In this paper the stability of the arsenic sulfide nanosuspension stabilized with Poloxamer 407 (PX407) was studied. PX407 is a nonionic surfactant composed of polyoxy- ethylene–polyoxypropylene triblock copolymers. It has a good solubilizing capacity and is considered a good medium for drug delivery systems with the least toxic properties of commercially available copolymers (Gilbert et al., 1986; Escobar-Chávez et al., 2006). It has been reported that both hydrophobic and hydrophilic properties of stabilizers are required for ensuring the appropriate stability. The driving force of the adsorption of stabilizers onto the surface of a hydrophobic drug is the hydrophobic moieties of the stabilizers. In the absence of adsorption, stabilization cannot occur, and no dispersed nanosuspensions can be obtained (Wang et al., 2013). The hydrophilic portion of the stabilizer tends to orient toward water providing an effective steric stabilization. In the case of PX407, central polyoxypropylene chain is hydrophobic (b) flanked by two hydrophilic chains of polyoxyethylene (a) (Fig. 1). * Corresponding author. Tel.: +421 557922607; fax: +421 557922604. E-mail address: bujnakova@saske.sk (Z. Buj  náková). http://dx.doi.org/10.1016/j.ijpharm.2014.11.043 0378-5173/ ã 2014 Elsevier B.V. All rights reserved. International Journal of Pharmaceutics 478 (2015) 187–192 Contents lists available at ScienceDirect International Journal of Pharmaceutics journal homepage: www.elsev ier.com/locate /ijpharm