Issue 1, 2021

Enhanced solubility, permeability, and tabletability of nicorandil by salt and cocrystal formation

Abstract

Cocrystallization is a rational selection crystal engineering approach for the development of novel solid forms with enhanced physicochemical and mechanical properties. Nicorandil (NCR) is a niacinamide vitamin derivative used to treat angina pectoris. A binary solid form screen of NCR with homologous dicarboxylic acids afforded NCR–oxalic acid (NCR–OA, 1 : 1), NCR–fumaric acid (NCR–FA, 1 : 1), NCR–succinic acid (NCR–SA, 1 : 1), and NCR–suberic acid (NCR–SBA, 1 : 0.5). The binary solids were characterized by powder X-ray diffraction, IR and NMR spectroscopy, and DSC. NCR–FA and NCR–SBA were crystallized by slow evaporation from chloroform and toluene solvents, respectively. Single crystal X-ray diffraction confirmed that NCR–FA is a molecular salt, while NCR–SBA is a neutral cocrystal. NCR and the FA anion are connected via the robust carboxylate⋯pyridinium synthon, whereas in the NCR–SBA cocrystal, the components associate via the carboxylic acid⋯pyridine synthon. The phase stability, solubility, dissolution rate, diffusion rate and tabletability studies have demonstrated that the binary solids exhibit improved physical and mechanical properties compared to the NCR drug. Specifically, the NCR–FA salt and NCR–SBA cocrystal have higher solubility, dissolution rate, and hardness at lower pressures, making the formulation suitable for tablet compression.

Graphical abstract: Enhanced solubility, permeability, and tabletability of nicorandil by salt and cocrystal formation

Supplementary files

Article information

Article type
Paper
Submitted
10 Қыр. 2020
Accepted
02 Қар. 2020
First published
03 Қар. 2020

CrystEngComm, 2021,23, 227-237

Enhanced solubility, permeability, and tabletability of nicorandil by salt and cocrystal formation

M. K. C. Mannava, A. Gunnam, A. Lodagekar, N. R. Shastri, A. K. Nangia and K. A. Solomon, CrystEngComm, 2021, 23, 227 DOI: 10.1039/D0CE01316A

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