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Curcumin (C), a natural anticancer agent suffers extremely low aqueous solubility and rapid systemic elimination, therefore, the aim from the present study was to develop and optimize biocompatible, biodegradable solid lipid nanoparticles containing curcumin (CSLNs) using Solvent Injection Method. The components selected to develop the SLNs were Glycerol MonoStearate (GMS; the lipidic carrier), Poloxamer 407 (P407; Surfactant) and Ethanol (solvent for the drug and the lipidic carrier). The combination and ratios for the optimization process were carried out using 2 3 full-factorial designs. The experimental design runs (8 formulations H1–H8) were prepared and the design dependent responses (assessment of particle size, Entrapment Efficiency % and the in vitro release study) were characterized. The developed formulae showed a nanometric particle size range (203.0– 345.0nm), high Entrapment Efficiency % (62.77–87.42 %) and prolonged release over 24 hr periods (55.97–89.64 %). These results were analyzed using JMP ® 10 software and its analytical tools were used to draw Pareto charts and the interactions plots. On the basis of the software analysis, formulation H9 with a desirability factor of 0.582 was selected as the optimized formulation and was evaluated for the dependent responses. Formulation H9 showed a particle size of 249.1 nm, 74.51 % Entrapment efficiency, 85.72 % in vitro release over 24 hr and these results suggested that the solid lipid nanoparticles formulations could be a promising method to sustain the release of curcumin. INTRODUCTION Traditional medicine is known to be fertile ground for the source of modern medicines (Corson and Crews, 2007; Aggarwal and Sung, 2008; Wu et al., 2011) as Nature’s chemical diversity and complexity form a unique source of molecules for a wide range of therapeutic targets (Balunas and Kinghorn, 2005; Coimbra et al., 2011). Several natural compounds at present are being appreciated because of their broad spectrum of activities making them more appropriate to interfere in multifactorial diseases, such as cancer (Nobili et al., 2009; Pan et al., 2009; Harvey et al., 2010). In addition, compared to synthetic compounds, natural bioactive compounds generally have better safety profiles, are well accepted by the public (opinion) and are usually relatively cheap (Pan et al., 2009; Gupta et al., 2010). However, their physicochemical properties are generally not drug-like and pose a number of challenges that need to be overcome for their establishment as effective therapeutics (Shoji and Nakashima, 2004; Nobili et al., 2009; Gupta et al., 2010; Coimbra et al., 2011). Az. J. Pharm Sci. Vol. 48, September, 2013. 85 A great example of these natural compounds is curcumin which has considerable potentials against various human diseases like cancer (Anand et al., 2007; Tsai et al., 2011; Yallapu et al., 2012). Though curcumin has demonstrated safety and efficacy profiles (as a chemotherapeutic agent) but it has restrictive pharmaceutical role because of its extremely low aqueous solubility and rapid systemic elimination which severely curtails its bioavailability profile (Anand et al., 2008; Anand et al., 2010; Mohanty and Sahoo, 2010). Therefore, design and development of biodegradable controlled drug delivery system for curcumin was the main research aspect on which extensive work has been done in the past few decades (Mulik et al., 2009). Solid Lipid Nanoparticles (SLNs) were developed as the first generation of Lipid based Nanoparticless and are being extensively studied as promising approaches for poorly soluble drugs (Almeida and Souto, 2007; Martins et al., 2007; Nayak et al., 2010). SLNs as drug delivery systems have a well known advantages such as good tolerability, lower cytotoxicity, higher bioavailability by oral administration, increase in the drug stability as well as other advantages provided by lipid excipients, such as biodegradability and cost effectiveness that promote their use as novel drug carriers (Mehnert and Mader, 2001; Mukherjee et al., 2007). Also since they are consisting of physiological and biodegradable lipids, lipid nanoparticles are suitable for the incorporation of lipophilic, hydrophilic, and poorly water-soluble drugs within the lipid matrix in considerable amounts (Bunjes et al., 2001). Lipidic carriers used to prepare SLNs can be highly purified lipids such as tristearin or tripalmitin, hard fats such as stearic acid or behenic acid, waxes such as cetyl palmitate, and acylglycerol mixtures such as compritol or GMS (Souto and Müller, 2006). The objectives behind the selection of GMS (a non-polar lipid, C21H42O4) as the lipid phase to formulate SLNs formulations were its high drug entrapment efficiency as the presence of high amounts of Mono-, Di-glycerides in GMS help the drug to solubilize in the lipid fraction as well as the less defined mixture of acylglycerol provides additional space for drug molecules to get entrapped (Manjunath et al., 2005; Shah and Pathak, 2010). In addition to that GMS depicts some surface tension activity due to the fact that it is composed of ~ 50% of Monoglycerides which was held responsible for the small particle size of GMS-based lipid nanoparticles in comparsion to other lipidic carriers such as Trimyristin and Tristerin which are triglycerides of higher molecular weight and lacking the surface tension activity (Jenning et al., 2000; Nayak et al., 2010). Poloxamers or Pluronic (marketed by BASF Corporation) are the series of commercially available difunctional triblock copolymers of non-ionic nature. They comprise of a central block of relatively hydrophobic polypropylene oxide surrounded on both sides by the blocks of relatively hydrophilic poly ethylene oxide and they are regarded as PEO-PPO-PEO copolymers (Kabanov et al., 2002). Among number of natural and synthetic polymers, Poloxamer 407 (P407), a US Food and Drug Administration-approved polymer, is the most attractive due to its biocompatibility, biodegradability as well as its low toxicity profile (Hussain and Saxena, 2012). Also P407 had been used to produce micellar formulations of different drugs to increase their solubility, their metabolic stability and their circulation time (Oh et al., 2004; Zhang et al., 2011; Hussain and Sexana, 2012). Furthermore, P407 had been used either alone or with other polymers like Carbopol 934 and HPMC to provide controlled release delivery systems of different drugs (Kabanov et al., 2002). The objective of the present study was to develop SLNs of curcumin and to optimize it for the independent variables selected (amount of glycerol monostearate, concentration of Az. J. Pharm Sci. Vol. 48, September, 2013. 86 poloxamer, and volume of ethyl alcohol) in order to achieve desired particle size with maximum entrapment efficiency (EE %) and percent cumulative drug release (CDR %). Factorial design enables all the factors to be varied simultaneously, allowing quantification of the effects caused by independent variables and interactions between them. Many researchers have optimized nanoparticulate formulations using 2 3 full-factorial design (Bozkir and Saka, 2005; Bhavsar et al., 2006; Derakhshandeh et al., 2007; Shah and Pathak, 2010). MATERIALS AND METHODS

APPLICATION OF 23 FULL-FACTORIAL DESIGN FOR DEVELOPMENT AND OPTIMIZATION OF BIOCOMPATIBLE, BIODEGRADABLE SOLID LIPID NANOPARTICLES CONTAINING CURCUMIN