Issue 13, 2019

On the prevalence of smooth polymorphs at the nanoscale: implications for pharmaceuticals

Abstract

We demonstrate, for four different systems of pharmaceutical relevance, that ball mill grinding leads to different polymorphic transformations depending on the milling conditions. In all four cases, the commercial polymorph converts to a different polymorph upon ball-mill neat grinding (NG). This transformation can be reversed by grinding the so obtained polymorph in the presence of small amounts of solvent (LAG), leading back to the commercial polymorph. Scherrer particle size determinations reveal that NG conditions almost always lead to smaller particle sizes in the nanometer length scales. Computational studies confirm that polymorphs obtained by the specific ball mill LAG conditions reported correspond to the lowest lattice energy forms. Our study further confirms our earlier conclusions that, at the nanoscale, polymorphs with higher lattice energies can become the thermodynamically stable forms if their surfaces are more stable than those of the polymorphs obtained by LAG. We found, however, one exception to this trend in D-sorbitol. We observe that polymorphs with smoother surfaces (low roughness) are usually the ones observed by NG. This observation points to a link between surface roughness and surface stability.

Graphical abstract: On the prevalence of smooth polymorphs at the nanoscale: implications for pharmaceuticals

Supplementary files

Article information

Article type
Paper
Submitted
12 Жел. 2018
Accepted
14 Ақп. 2019
First published
14 Ақп. 2019

CrystEngComm, 2019,21, 2203-2211

On the prevalence of smooth polymorphs at the nanoscale: implications for pharmaceuticals

A. M. Belenguer, A. J. Cruz-Cabeza, G. I. Lampronti and J. K. M. Sanders, CrystEngComm, 2019, 21, 2203 DOI: 10.1039/C8CE02098A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements