Metal oxide foams for pharmaceutical amorphization

Jan Gröls, Thais Tasso Guaraldo, Carmelo Herdes, Davide Mattia, Bernardo Castro Dominguez

Research output: Contribution to journalArticlepeer-review


The amorphization of pharmaceutical crystals is an effective strategy to enhance the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). However, this process can be challenging as these supramolecular structures arrange mainly via hydrogen bonds and π-π interactions. In this work, we propose that porous metal oxides can be used to promote the amorphization of APIs. In particular, zinc oxide foams were synthesized, characterized, and used to induce the production of amorphous paracetamol, via solvent evaporation. Amorphous paracetamol was generated inside the pores of the foam, whereas its crystalline form type I appeared on the bulk of the crystallization media. The interaction of paracetamol with zinc oxide was analyzed through zeta potential measurements and molecular dynamics simulations. The results of this work suggest that the porous 3D structure of metal oxide foams prevents nucleation, hinders hydrogen bonding, and therefore generates amorphous structures. This work demonstrates for the first time (i) the co-amorphization of PCM/MCM mixtures, (ii) how confinement and surface energy induce disruptions in crystal structure, and (iii) the performance of metal oxides as stabilizers for amorphous structures. We propose that metal oxide additives during crystallization are a novel technique that will aid in developing amorphous structures with enhanced pharmacological efficiencies than those found in native crystalline APIs.

Original languageEnglish
Pages (from-to)3457-3464
Number of pages8
Issue number18
Early online date12 Apr 2022
Publication statusPublished - 14 May 2022
Externally publishedYes


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