Evaluation of Indomethacin Percutaneous Absorption From Nanostructured Lipid Carriers (NLC): In Vitro and In Vivo Studies MAURIZIO RICCI, 1 CARMELO PUGLIA, 2 FRANCESCO BONINA, 2 CATERINA DI GIOVANNI, 2 STEFANO GIOVAGNOLI, 1 CARLO ROSSI 1 1 Department of Chemistry and Technology of Drugs, School of Pharmacy, University of Perugia, Perugia, Italy 2 Department of Pharmaceutical Sciences, School of Pharmacy, University of Catania, Catania, Italy Received 21 July 2004; revised 2 December 2004; accepted 2 February 2005 Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jps.20335 ABSTRACT: The aim of this study was the evaluation, in vitro and in vivo, of indomethacin (IND) release through the skin from nanostructured lipid carriers (NLC). NLC were prepared by ultrasonication, and were characterized in order to determine drug content, and particle size; finally the NLC were processed to hydrogels (A and B). The IND release pattern from NLC hydrogels was evaluated in vitro, to determine its percutaneous absorption through excised human skin (stratum corneum and epidermis, SCE), and in vivo. To evaluate the in vivo IND release, two methods were employed: (1) the IND topical anti-inflammatory activity was determined at different timepoints after its cutaneous application; in this case, the UVB-induced erythema on healthy human volunteers, chosen as inflammatory model, was monitored by reflectance visible spectrophotometry; (2) the extent of IND absorption into human skin was performed by the tape-stripping technique. The in vitro percutaneous absorption studies showed lower fluxes of IND through SCE membranes from NLC hydrogels (A and B) in comparison to an aqueous dispersion (C) and a hydro-alcoholic gel (D) both containing free IND. The findings from the former in vivo method showed that the anti-inflammatory effect, following IND topical application, was more prolonged with IND-loaded NLC gel formulation (A) if compared to formulation C and D. The results from tape stripping technique confirmed the trend obtained by the former in vivo method and indicated that IND topical bioavailability in the stratum corneum varied substantially depending upon the formulations (A–D). ß 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:1149–1159, 2005 Keywords: indomethacin; NLC; in vitro and in vivo studies; skin; controlled release; reflectance spectrophotometry; tape-stripping technique; particle size; ultrasound; Franz cell INTRODUCTION In recent years, the study of bioactive agent controlled release through the skin attracted the attention of many researchers all over the world. Different vehicles, ranging from liposomes, 1 multiple emulsions 2 to polymeric nanoparticles, 3 have been developed and interesting drug release profiles have been obtained. Solid lipid nanoparticles (SLN), and more recently nanostructured lipid carriers (NLC), have been studied as an interesting alternative to these traditional colloidal carriers especially for the delivery of lipophilic compounds. Although both carrier types are submicron size particles (50–1000 nm) and are based on solid JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 94, NO. 5, MAY 2005 1149 Correspondence to: Carmelo Puglia (Telephone: þ39957384273; Fax: þ3995222239; E-mail: capuglia@unict.it) Journal of Pharmaceutical Sciences, Vol. 94, 1149–1159 (2005) ß 2005 Wiley-Liss, Inc. and the American Pharmacists Association