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Synlett 2020; 31(16): 1573-1580
DOI: 10.1055/s-0040-1707139
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© Georg Thieme Verlag Stuttgart · New York

Leveraging Framework Instability: A Journey from Energy Storage to Drug Delivery

Kuthuru Suresh 
a   Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA
,
Vilmalí López-Mejías 
a   Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA
,
Saikat Roy 
a   Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA
,
Daniel F. Camacho 
a   Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA
,
Adam J. Matzger  ∗
a   Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA
b   Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI 48109-1055, USA   Email: matzger@umich.edu
› Author AffiliationsThis work was supported by the United States Department of Energy (DE-SC0004888).
Further Information

Publication History

Received: 11 April 2020

Accepted after revision: 14 May 2020

Publication Date:
18 June 2020 (online)

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Abstract

Amorphous pharmaceuticals often suffer from poor physical stability, which can negate their high solubility, fast dissolution rate, and better oral bioavailability vs. crystalline forms. This represents a major hurdle to processing, storage, and delivery of amorphous pharmaceuticals. Several approaches to addressing these problems have been pursued, but there is still a need for a general method for stabilizing the amorphous form. We describe a novel approach using a water-unstable metal-organic framework as a drug delivery vehicle that demonstrates improved amorphous form stability accompanied by remarkably enhanced solubility and a fast dissolution rate. This research project spanned eleven years from conception to realization and dissemination. With origins in understanding the stability or porous solids for energy storage materials, the work also highlights potential of basic science understanding to illuminate new areas of application.

Key words

pharmaceuticals - amorphous form - metal-organic frameworks - stability - solubility and dissolution rate
 

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