A Drug-Drug Multicomponent Crystal of Metformin and Dobesilate: Crystal Structure Analysis and Hygroscopicity Property

Lan Jiang; Xiangnan Hu; Linhong Cai

doi:10.3390/molecules27113472

A Drug-Drug Multicomponent Crystal of Metformin and Dobesilate: Crystal Structure Analysis and Hygroscopicity Property

Molecules. 2022 May 27;27(11):3472. doi: 10.3390/molecules27113472.

Authors

Lan Jiang¹, Xiangnan Hu², Linhong Cai²

Affiliations

¹ College of Environment and Resources, Chongqing Technology and Business University, Chongqing 400067, China.
² Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.

Abstract

A drug-drug multicomponent crystal consisting of metformin (MET) and dobesilate (DBS) was prospectively connected by solvent cooling and evaporating co-crystallization using the multicomponent crystal strategy, not only to optimize the physicochemical properties of single drugs, but also to play a role in the cooperative effect of DBS with the potential vascular protective effects of MET against diabetic retinopathy (DR). The crystal structure analysis demonstrated that MET and DBS were coupled in a 3D supramolecular structure connected by hydrogen-bonding interactions with a molar ratio of 1:1. Almost all hydrogen bond donors and receptors of MET and DBS participated in the bonding, which hindered the combination of remaining potential hydrogen bond sites and water molecules, resulting in a lower hygroscopicity property than MET alone.

Keywords: diabetic retinopathy; dobesilate; drug–drug multicomponent crystal; hydrogen-bonding interactions; hygroscopicity property; metformin.

MeSH terms

Crystallization
Hydrogen Bonding
Metformin* / chemistry
Water / chemistry
Wettability

Substances

Water
Metformin

Grants and funding

The authors acknowledge the financial support received from the Chongqing Science and Technology Commission (cstc2019jscx-msxmX0096). We also appreciate that the undergraduate Everyone Innovation Program of the School of Pharmacy of Chongqing Medical University (DXSZCXM201905) provides partial financial aid for our work.