Drug-inorganic matrix composites studied by solid state NMR

Many active pharmaceutical ingredients (APIs) show a limited and variable bioavailability mainly associated to inadequate biopharmaceutical properties such as aqueous solubility and dissolution rate. The latter is the main factor responsible for the limited efficacy of many biopharmaceutics classification system (BCS) class II and class IV orally administered drugs. In this context, the employment of inorganic matrices, such as mesoporous materials and lamellar anionic clays, for the preparation of host-guest composites is a suitable strategy for improving biopharmaceutical properties [1]. Indeed, some inorganic matrices are able to host drugs into nanometric galleries or pores in non-crystalline form. In this way rapid dissolution can occur after the contact with the dissolution medium, without the need of a previous modification of the API chemical structure. The characterization of the solid form and chemical environment of the API in this kind of formulations therefore appears particularly important. In this work Solid State NMR (SS NMR) techniques have been applied in order to investigate two different composites, containing ibuprofen as BCS class II guest API and Hallosites NanoTubes (HNT) [2] and Hydrotalcite (HTlc) anionic clays [3] as inorganic hosts. On one hand, experiments on 13C nuclei allowed us to obtain information on ibuprofen in the ?formulations. On the other hand, experiments on 29Si and 27Al nuclei gave insights into the properties of the inorganic matrices. Moreover, experiments on 1H nuclei allowed both the organic and inorganic components to be inspected. The comparison of spectral and relaxation properties of the composites with respect to those of the pure components allowed interesting differences, especially on the dynamics of ibuprofen, to be highlighted and discussed. [1] L. Perioli, C. Pagano, Expert Opin. Drug Deliv. 9, 1559-1572 (2012). [2] P. Pasbakhsh, G. J. Churchman, J. L. Keeling Appl. Clay Sci. 74, 47-57 (2013); D. Tan, P. Yuan, F. Annabi-Bergaya, H. Yu, D. Liu, H. Liu, H. He Micropor. Mesopor. Mat. 179, 89-98 (2013). [3] E. Conterosito, W. Van Beek, L. Palin, G. Croce, L. Perioli, D. Viterbo, G. Gatti, and M. Milanesio, Cryst. Growth Des. 13, 1162-1169 (2013).