Industrial Crops and Products 59 (2014) 309–317 Contents lists available at ScienceDirect Industrial Crops and Products jo ur nal home p age: www.elsevier.com/locate/indcrop Comparison of Box–Behnken and central composite designs in optimization of fullerene loaded palm-based nano-emulsions for cosmeceutical application Ngan Cheng Loong a,∗ , Mahiran Basri a,b,∗ , Lye Fui Fang a , Hamid Reza Fard Masoumi a , Minaketan Tripathy c , Roghayeh Abedi Karjiban a , Emilia Abdul-Malek a a Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia b Halal Products Research Institute, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia c Laboratory of Fundamentals of Pharmaceutics, Faculty of Pharmacy, Puncak Alam Campus Universiti Teknologi MARA (UiTM), 42300 Selangor, Malaysia a r t i c l e i n f o Article history: Received 18 February 2014 Received in revised form 22 May 2014 Accepted 29 May 2014 Keywords: Nano-emulsions Fullerene Response surface methodology (RSM) Central composite rotatable design (CCRD) Box–Behnken design (BBD) a b s t r a c t Box–Behnken (BBD) and central composite rotatable designs (CCRD) were used as statistical multivariate methods in the formulation optimization of fullerene loaded nano-emulsions. Effect of palm kernel oil ester (10–20%, w/w), emulsifier (5–10%, w/w) and xanthan gum (0.6–1.0%, w/w) as formulation variables on the particle size, -potential and viscosity of the nano-emulsions were investigated. Under the opti- mum conditions, CCRD model predicted the response values for particle size, -potential and viscosity were 153.6 nm, -53.4 mV and 42.1 Pa s, respectively. Nonetheless, BBD model suggested that the opti- mum conditions for a fullerene loaded nano-emulsion would gave particle size, -potential and viscosity of 151.6 nm, -53.8 mV and 43.1 Pa s, respectively. The actual response according to suggested composi- tions for both models showed excellent agreement with the predicted value with residual standard error (RSE) of less than 4%. Optimum nano-emulsions were stable during storage at 25 and 45 ◦ C for 90 days and freeze–thaw cycle. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Generation of free radicals in the human skin is the primary cause of various oxidative stress-related diseases, especially skin cancers, skin aging and acne vulgaris (Zouboulis and Makrantonaki, 2011; Reuter et al., 2010; Sarici et al., 2010). Oxidative stress in skin is common due to the reactive oxygen species (ROS) produced under the influence of environment or within the skin. Human skin is often exposed to harsh environments such as ultraviolet (UV) radiation from the sun and environmental pollutants. Upon UV exposure, free radicals and ROS induce the production of lipid radi- cals which are held accountable for the damaged cell membrane and ultimately lead to cell death (Herrling et al., 2006; Matsumura and Ananthaswamy, 2004). Protection against oxidative stress is ∗ Corresponding authors at: Department of Chemistry, Faculty of Science, Univer- siti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. Tel.: +60 389466603; fax: +60 389432508. E-mail addresses: clngan88@yahoo.com (C.L. Ngan), mahiran@upm.edu.my (M. Basri). possible in the presence of antioxidant. Antioxidants are able to neutralize the free radicals by pairing with another electron of the oxygen molecule in the stabilization process. Fullerene is the third carbon allotrope, after graphite and diamond, which was discovered in 1985 (Kroto et al., 1985). Fullerene has radical scavenging activity where 30 carbon–carbon double bonds can undergo addition reaction with free radicals (McEwen et al., 1992; Krusic et al., 1991). Research on fullerene has received tremendous attention upon its remarkable antiox- idant activity (Wang et al., 1999). Fullerene may offer a better alternative as potent biological antioxidant in the pharmaceuti- cal and cosmetic industry. In addition, fullerene was proven to be non-toxic and safe (Aoshima et al., 2009; Mori et al., 2006; Gharbi et al., 2005). Application of fullerene in related industries has been hampered by its hydrophobicity, hence efforts were car- ried out to solve the complication. Different approaches have been attempted to solubilize fullerene in water such as surface mod- ification of fullerene, surfactant aided method, solvent exchange method and long term stirring (Markovic and Trajkovic, 2008; Lyon et al., 2006; Oberdorster et al., 2006; Bosi et al., 2003). However, it would be cost ineffective to be produced in large scale. http://dx.doi.org/10.1016/j.indcrop.2014.05.042 0926-6690/© 2014 Elsevier B.V. All rights reserved.