**1. Introduction**

Ketoprofen (KET) is one of the most common NSAIDs (Nonsteroidal anti-inflammatory drugs) used for relieving pain in many acute and chronic conditions as musculoskeletal, tendinitis, strain, sprain, trauma, and arthritis [1,2]. However, its efficacy, especially in topical therapies, is impaired due to both the very poor water solubility (KET is labeled in class II of the biopharmaceutics classification system, BCS) and photochemical instability [3,4].

KET exposition to UV radiations, especially UVA, is responsible for phototoxic and photoallergic reactions [5,6]. These reactions are due to radical intermediates generated by KET-UV rays interactions responsible for DNA damage, mitochondria depolarization, and lysosomes destabilization [6–8]. Thus, KET topical administration by conventional formulations, such as gels, emulgels, creams, sprays, and foams, does not guarantee protection from UV radiation, exposing the patient to serious health problems [9]. Moreover, conventional formulations are responsible for a limited residence time of the drug in the application site.

Thus, in order to exploit the benefits of KET and to overcome these problems, it is necessary to find a suitable formulation able to protect it from sunlight and to improve the residence time.

With this aim, many approaches have been purposed mainly based on KET entrapment in supramolecular structures as cyclodextrins, liposomes, niosomes, microparticles [10–12]. A further interesting approach is represented by the realization of host-guest complexes using an inorganic matrix as the anionic clay hydrotalcite (HTlc) [13]. This material shows the typical lamellar structure able to store anionic molecules (guest) in the nanosized interlamellar space (host) [14].

The general formula of synthetic HTlc is [M(II)1−xM(III)x(OH)2] <sup>x</sup>+(An−x/n) <sup>x</sup><sup>−</sup> mS, where M(II) is a divalent metal cation (usually Mg, Zn); M(III) is a trivalent metal cation (usually Al, Fe); generally, the *x* value, M(III)/M(II) + M(III), ranges between 0.25 and 0.33; An<sup>−</sup> is an exchangeable inorganic or organic anion, which compensates the positive charge of the layer; m is the mol of solvent S, usually water, co-intercalated per mole of compound [13]. The intercalation of an organic molecule (drug) into HTlc lamellae allows obtaining a new inorganic-organic hybrid product with enhanced properties in terms of solubility [15,16], photoprotection [17–19], and physical and chemical stability [20]. These lamellar materials represent a valuable strategy in developing formulations with prolonged efficacy, thanks to the double control of the release and protection of the guest.

The aim of this work was to purpose a new formulation in which KET is stabilized from UV light, able to be applied on skin without adhesives, and to stay there for a prolonged time. Therefore, the photoprotective effect of the lamellar clay ZnAl-HTlc towards KET, once intercalated into the lamellae (ZnAl-KET), was investigated. Moreover, the performances of a self-adhesive/biocompatible patch loaded with the intercalation product ZnAl-KET were evaluated in terms of mechanical properties, bioadhesion, and drug release capability.
