**2. Materials and Methods**

## *2.1. Materials*

Ketoprofen acid form (KETH) and sodium salt (KET-Na) were purchased from Sigma-Aldrich (Milano, Italy). Glycerol and urea were purchased from Acef S.p.A. (Fiorenzuola D'Arda, Piacenza, Italy). Aluminum chloride esahydrate, calcium chloride, potassium dihydrogen phosphate, sodium hydrogen phosphate, polyvinilpyrrolidone, potassium carbonate (Carlo Erba, Cornaredo, Milano, Italy) were supplied by DueM (Perugia, Italy). Zinc oxide was supplied by Caelo (Hilden, North-Rhine Westphalia, Germany). Sodium carboxymethycellulose (NaCMC) was supplied by Hercules Inc.—Aqualon division (Wilmington, DE, USA).

Ultrapure water was obtained by reverse osmosis process in a MilliQ system Millipore (Roma, Italy). Other reagents and solvents were of analytical grade and used without further purification.

## *2.2. Hydrotalcite Synthesis*

ZnAl-HTlc in carbonate form was obtained by coprecipitation of Zn(II)-Al(III), accomplished by the hydrolysis of urea. The nitrate form ZnAl-HTlc-NO3 (ZnAl-NO3) was obtained, treating the solid with a diluted solution of the corresponding mineral acid [21].

## *2.3. Hybrid Preparation*

The hybrid ZnAl-KET was prepared by ion-exchange mechanism according to previous work [15]. A carbon dioxide-free NaOH water solution 0.1 M was added to a suspension of KET (0.1 M). Then, ZnAl-NO3 was added to the obtained salt solution (molar ratio HTlc/KET 1:2). The suspension was kept under magnetic stirring (600 rpm) for 24 h at room temperature. The solid (ZnAl-KET) was

recovered by centrifugation (A.L.C. centrifuge. mod. 4236A. Milano, Italy), washed with carbonate free water, and dried at room temperature under P2O5.
