Solid-state salification and mechanochemical activation of poorly bioavailable drugs

The "mechanochemical" process is a solvent-free process which consists in the conversion of mechanical energy into chemical energy: due to the mechanical treatment (mostly realized in high-energy mills), physical and/or chemical transformations are induced in the solid molecules.

Hence, the mechanical treatment may be used to prepare pharmaceutical solids in an extremely "active" metastable state (eg. nanocrystals, amorphous solids, solids with crystalline defects) stabilized by interactions with the polymeric carrier during co-milling, or for synthesis ("dry synthesis") of a more soluble salt realized in the presence of a polymeric carrier that acts, in this case, as a solid vehicle. The final product is highly in vitro and in vivo bioavailable and therefore the process is very suitable for poorly- soluble active ingredients suffering for poor in vivo absorption (see figure).

Mechanochemistry is also an effective method for the preparation of multicomponent crystal systems and for the deracemization of racemic compound/mixtures.  Also in these perspectives the presence of a polymer (Polymer-assisted grinding- POLAG) can be useful for improving reaction rate and for increasing product diversity, as demonstrated in the case of mechanochemical cocrystallization reactions (see figure)

 

Collaborations: M. Grassi (Dept. Engineering and Architecture), Francesco Princivalle (Dept. Maths/Geosciences), Davide Lenaz (Dept. Maths/Geosciences), Sergio Invernizzi  (Dept. Life Sciences), Cinzia Cepek (TASC, Area Science Park),  Elvio Carlino (TASC, Area Science Park), Roberto Gobetto (Univ. of Turin), Michele Chierotti (Univ. of Turin), Erica Franceschinis (Univ. of Padua), Stefano Dall’Acqua (Univ. of Padua), Nadia Passerini (Univ. Bologna), Beatrice Albertini (Univ. Bologna), Iztok Grabnar (Univ. Ljubljiana), Gabriela Schneider Rauber (Univ. Cambridge), William Jones (Univ. Cambridge).

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Last update: 08-23-2019 - 19:50