Conventional or mechanochemically-aided intercalation of diclofenac and naproxen anions into the interlamellar space of CaFe-layered double hydroxides and their application as dermal drug delivery systems
Márton Szabados, Attila Gácsi, Yvette Gulyás, Zoltán Kónya, Ákos Kukovecz, Erzsébet Csányi, István Pálinkó, Pál Sipos
Abstract
The intercalation/encapsulation of the anionic forms of diclofenac and naproxen anti-inflammatory drugs into CaFe-layered double hydroxides (LDHs) were investigated by four techniques. A novel mechanochemically-aided pathway was used and compared to the conventional co-precipitation, direct anion exchange and dehydroxylation-rehydration routes. The evolved average crystal thicknesses (23–35 nm) showed good correlation with the high drug-loading content (26–55% w/w) of the LDH solids. The as-prepared hybrid nanocomposites were studied in detail by X-ray diffractometry, Fourier-transform infrared and Raman spectroscopies, scanning electron microscopy, thermogravimetric and dynamic light scattering analyses. The drug−LDH solids were dispersed in hydrogels and the light microscopic size analysis imaged particles mainly of area between 5 and 10 μm2. In Franz diffusion cells, the in vitro drug release tests (collated by the Korsmeyer–Peppas kinetic model) registered slow release of the organic molecules from the external surface and the interlayer region of the LDH particles highly depending on the applied intercalation techniques. Compared to hydrogels without LDH solids, the liberation of drug molecules were found to be 15–70% slower from their LDH-capsulated forms. Raman mapping of the ex vivo human skin penetration tests visualized the transdermal route of the drug molecules and attested their accumulation in the epidermis and upper zone of the dermis from the LDH − hydrogel preparations.