Available online at www.sciencedirect.com International Journal of Pharmaceutics 346 (2008) 124–132 Pharmaceutical Nanotechnology Nanostructured lipid carrier (NLC) based gel of celecoxib Medha Joshi, Vandana Patravale ∗ Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology (Autonomus), N.P. Marg, Matunga, Mumbai 400019, India Received 13 March 2007; received in revised form 29 May 2007; accepted 29 May 2007 Available online 15 June 2007 Abstract Nanostructured lipid carriers (NLC) based topical gel of celecoxib was formulated for the treatment of inflammation and allied conditions. NLC prepared by the microemulsion template technique were characterized by photon correlation spectroscopy for size and scanning electron micrograph (SEM) studies. Drug encapsulation efficiency was determined using Nanosep ® centrifugal device. The nanoparticulate dispersion was suitably gelled and assessed for in vitro release and in vitro skin permeation using rat skin. Efficacy of the NLC gel was established using a pharmacodynamic study, i.e., aerosil-induced rat paw edema model. The skin permeation and rat paw edema pharmacodynamic studies were carried out in comparison with a micellar gel which had the same composition as that of the NLC gel except for the solid lipid and oil. The NLC based gel described in this study showed faster onset and elicited prolonged activity until 24 h. © 2007 Elsevier B.V. All rights reserved. Keywords: Celecoxib; Nanosturctured lipid carriers (NLC); Topical gels; Micellar; Anti-inflammatory; Prolonged action 1. Introduction In the last decade, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been looked upon as promising carriers for presenting several attractive features for transdermal drug delivery. SLN are identical to an oil-in- water emulsion, except that the liquid lipid (oil) portion of the emulsion is replaced by a solid lipid having a mean photon correlation diameter (PCS) ranging between 80 and 1000 nm (M¨ uller et al., 2000a). SLN are particles made from solid lipids or lipid blends and are produced by one of the follow- ing techniques, namely, high pressure homogenization (M¨ uller and Lucks, 1996), microemulsion template technique (Gasco, 1993), solvent emulsification evaporation technique (Sj¨ ostr¨ om and Bergenst˚ ahl, 1992), solvent displacement technique (Hu et al., 2002; Schubert and M¨ uller-Goymann, 2003), solvent emulsification diffusion method (Trotta et al., 2003; Quintanar- Guerrero et al., 2005), phase inversion (Heurtault et al., 2002) and a very recently introduced membrane contractor technique (Charcosset et al., 2005; Ahmed El-Harati et al., 2006). NLC, the new generation of lipid nanoparticles, overcome the limita- tions associated with the SLN, namely, limited drug loading, ∗ Corresponding author. Tel.: +91 22 24145616; fax: +91 22 24145614. E-mail address: vbp muict@yahoo.co.in (V. Patravale). risk of gelation and drug leakage during storage caused by lipid polymorphism (M¨ uller et al., 2000b). NLC consists of a mixture of spacially very different lipid molecules, i.e., solid lipid(s) is blended with liquid lipid(s) (oils) (M¨ uller et al., 2004). The resulting matrix of the lipid particles shows a melting point depression compared to the original solid lipid; however, the matrix remains solid at body temperature (M¨ uller et al., 2002a). Both SLN and NLC possess numerous features that are advantageous for topical route of application (M¨ uller et al., 2000c, 2002a,b; Mehnert and M¨ ader, 2001). SLN and NLC are colloidal carrier systems providing controlled release profiles for many substances (M¨ uller et al., 1995; Zur Muhlen et al., 1998; Souto et al., 2004; Souto and M¨ uller, 2005). These carriers are composed of physiological and biodegradable lipids exhibiting low systemic toxicity and low cytotoxicity (M¨ uller et al., 1997). Most of the used lipids have an approved status or are excipients used in commercially available topical cosmetic or pharmaceu- tical preparations. The small size of the lipid particles ensures close contact to stratum corneum and can increase the amount of drug penetrating into mucosa or skin. Due to their solid lipid matrix, a controlled release from these carriers is possible. This becomes an important tool when it is necessary to supply the drug over prolonged period of time, to reduce systemic absorp- tion, and when drug produces irritation in high concentrations. As a result of film formation after topical application, occlusive 0378-5173/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2007.05.060