Mg,Al layered double hydroxides with intercalated indomethacin: Synthesis, characterization, and pharmacological study


Magnesium aluminium layered double hydroxides (LDH) with a molar Mg/Al ratio of 2.0 have been prepared with intercalated indomethacin following two routes: reconstruction from a previously calcined Mg2Al-CO3 LDH, and coprecipitation from the corresponding chlorides. The solids have been characterized by powder X-ray diffraction, FTIR, and C-13 CP/MAS NMR spectroscopies and thermal stability (differential thermal analysis and thermogravimetric analysis). Intercalation of the drug is attained by both routes; however, while coprecipitation leads to a single layered structure, contamination with another layered MgAl-CO3 phase occurs by the reconstruction method. The amount of drug intercalated, as well as the heigth of the gallery, are larger by the coprecipitation than by the reconstruction one. The data obtained support a somewhat tilted, upwards orientation of the drug molecules forming an interdigited bilayer, in the case of the sample prepared by coprecipitation, with the carboxylate groups pointing towards the hydroxyl layers. However, in the case of the sample prepared by reconstruction, the molecules are forming a tilted, upwards monolayer. The solids prepared are stable up to 250degreesC. Pharmacological studies in vivo show that intercalation of the drug in the LDH reduces the ulcerating damage of the drug. (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association.




Pharmacology & Pharmacy; Chemistry


Del Arco, M; Cebadera, E; Gutierrez, S; Martin, C; Montero, MJ; Rives, V; Rocha, J; Sevilla, MA

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