Nanostructured Lipid Carrier Gel for the Dermal Application of Lidocaine: Comparison of Skin Penetration Testing Methods

Abstract

The aim of this research was to investigate the stability of a lidocaine-loaded nanostructured lipid carrier dispersion at different temperatures, formulate a nanostructured lipid carrier gel, and test the penetration profile of lidocaine from the nanostructured lipid carrier gel using different skin penetration modeling methods. The formulations were characterized by laser diffraction, rheological measurements and microscopic examinations. Various in vitro methods were used to study drug release, diffusion and penetration. Two types of vertical Franz diffusion cells with three different membranes, including cellulose, Strat-M®, and heat separated human epidermis were used and compared to the Skin-parallel artificial membrane permeability assay (PAMPA) method. Results indicated that the nanostructured lipid carrier dispersion had to be gelified as soon as possible for proper stability. Both the Skin-PAMPA model and Strat-M® membranes correlated favorably with heat separated human epidermis in this research, with the Strat-M® membranes sharing the most similar drug permeability profile to an ex vivo human skin model. Our experimental findings suggest that even when the best available in vitro experiment is selected for modeling human skin penetration to study nanostructured lipid carrier gel systems, relevant in vitro/in vivo correlation should be made to calculate the drug release/permeation in vivo. Future investigations in this field are still needed to demonstrate the influence of membranes and equipment from other classes on other drug candidates.

Novel In Vitro Investigational Methods for Modeling Skin Permeation: Skin PAMPA, Raman Mapping

“…The top plate was loaded with a fresh receptor solution of 250 µL, and a stirring bar was also used in each well. The Gut-Box™ from Pion, Inc. was used for stirring; the sandwich was incubated at 32 • C. The receptor solution was analyzed after 0.5, 1, 2, 3, 4, 5 and 6 h of incubation [21]. The quantity of DFNa was measured with UV spectroscopy at 275 nm using a SPECTROstarNano UV plate reader by BMG LABTECH GmbH (Ortenberg, Germany).…”

“…It is a 96-well plate-based method so it is a fast, low-cost and high-throughput method. So far, there have been few measurement results, but they are encouraging [16][17][18][19][20][21][22].…”

Semisolid Dosage

“…Four of the remaining articles deal with the investigation of skin penetration and permeation. Zsikó et al provide a "Comparison of Skin Penetration Testing Methods based on a Nanostructured Lipid Carrier (NLC) Gel for the Dermal Application of Lidocaine" [8]. As expected, drug release profiles of the Lidocaine-NLC gel obtained with the different techniques were not fully equivalent.…”

Alternatives to Biological Skin in Permeation Studies: Current Trends and Possibilities

“…A comparative study looking at the permeation of lidocaine from a nanostructured lipid carrier was conducted in a skin-PAMPA model and the Strat-M™. Both membranes correlated favorably with the heat-separated human epidermis in this study, with the Strat-M™ membrane sharing the most similarity in drug permeability profile to an ex vivo human skin model [108]. A summary of recent publications utilizing the Strat-M™ membrane in permeation studies is presented in Table 2.…”