Development and Optimization of a Nanostructured Lipid Carrier Based Gel Formulation of Etoricoxib for Topical Delivery Using Box-Behnken Design: In Vitro and Ex Vivo Evaluation

摘要

The objective of present research work was to develop, optimize and evaluate a nanostructured lipid carrier (NLC) based gel formulation of etoricoxib (ETXB) for better management of inflammatory conditions. The NLC was prepared by microemulsion template technique and optimized by a three-factor, three-level Box-Behnken design using particle size (nm), entrapment efficiency (EE, %), flux (mu g/cm(2)/h) as dependent variables and mixed lipid, surfactant mixture, drug concentration as independent variables. The optimized NLC dispersion was characterized by Transmission Electron Microscopy, Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry, X-ray Diffractometry and Confocal Laser Scanning Microscopy. The optimized NLC dispersion was suitably gelled and compared with a micellar gel for in vitro release and ex vivo studies using rat skin. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of ETXB from NLC gel. The NLC gel of ETXB showed less permeation as compared to micellar gel. The deposition potential and average of ETXB retained on skin from NLC gel were found to be higher as compared those achievable with the micellar gel. Skin irritation studies revealed that NLC gel of ETXB was safe, well tolerable and less irritant to the skin. It was concluded that developed NLC gel of ETXB holds promise for prolonged availability of ETXB in the skin tissues and safety for long term management of inflammatory conditions.