Formulation Optimization and In-vitro and In-vivo Evaluation of Lornoxicam Ethosomal Gels with Penetration Enhancers

Background: Ethosomes, a novel type of percutaneous drug delivery carrier with a lipid bilayer structure, penetrate the skin barrier due to their deformability and malleability, and presence of ethanol that fluidizes lipids in the skin. In order to further enhance the delivery of drugs through the skin, penetration enhancers are widely used. Objective: The objective of this work was to develop an optimized formulation of lornoxicam ethosomal gels, investigate skin permeability with the addition of penetration enhancers, and evaluate the invivo pharmacodynamics of these formulations. Methods: Lornoxicam ethosomes were prepared by the ethanol injection method and optimized using the orthogonal design method. Lornoxicam ethosomal gels with enhancers were prepared and optimized using in-vitro transdermal delivery experiments. Experiments on lornoxicam ethosomal gels containing various enhancers such as azone, menthol, lauryl alcohol, and oleic acid were conducted using vertical Franz diffusion cells to measure the percutaneous permeability of the different formulations. Furthermore, the in-vivo analgesic effects of the optimized lornoxicam ethosomal gels were examined using the hot-plate and acetic acid-induced writhing tests. Anti-inflammatory activity was investigated using the dimethylbenzene-induced mouse ear swelling method. Results: The results showed that compared to other formulations, the optimized lornoxicam ethosomal gels with 5 % menthol significantly increased transdermal penetration. Meanwhile, the optimized lornoxicam ethosomal gels showed remarkably anti-nociceptive and anti-inflammatory activity compared with the plain lornoxicam gels. Conclusion: These results suggest that the optimized ethosomal gel formulated in this study is a promising lornoxicam carrier in transdermal delivery systems to enhance anti-nociceptive and antiinflammatory efficiency.