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
Early online date11 Apr 2022
Publication statusPublished - 14 May 2022

Bibliographical note

Funding Information:
This research was supported by Royal Society-Research Grant RSG\R1\180090. Jan Gröls (JG) would like to thank the University of Bath for his Ph.D. studentship and the Centre for Doctoral Training in Sustainable Chemical Technologies. The authors also acknowledge EPSRC for funding (Grant No. EP/P031382/1). The authors gratefully acknowledge the Material and Chemical Characterization Facility (MC2) at the University of Bath for technical support and assistance in this work. Moreover, we would like to acknowledge Dr. Daniel Fonseca for his contribution, sketching the graphical abstract of this work.

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics


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