Issue 29, 2013

Novel solid forms of the anti-tuberculosis drug, Isoniazid: ternary and polymorphic cocrystals

Abstract

Novel cocrystals of an anti-tuberculosis drug, Isoniazid (INH), with pharmaceutically acceptable coformers such as nicotinamide (NA), 4-hydroxybenzoic acid (HBA), fumaric acid (FA), and succinic acid (SA) are reported. Cocrystallization experiments involving INH and HBA produced two polymorphs of a novel hydrate of the INH·HBA cocrystal. Similarly, cocrystallization of INH and FA produced a novel polymorph of the reported INH·FA cocrystal. We have successfully explored the idea of designing ternary cocrystals involving INH with NA and FA or SA. All the novel solids were thoroughly characterized and their crystal structures determined. All the crystal structures feature an acid–pyridine heterosynthon involving INH and the carboxylic acid. Stability of the novel cocrystals was evaluated by slurry experiments and dynamic vapor sorption studies. In addition, stability of the cocrystals at accelerated test conditions (40 °C, 75% RH) was also tested. Anhydrous INH·HBA cocrystal and Form I of INH·HBA cocrystal hydrate were found to convert to Form II of the INH·HBA hydrate, and Form II of INH·FA cocrystal converted to Form I of the INH·FA cocrystal. Ternary cocrystals remain stable at all test conditions. Solubility and dissolution experiments revealed a greater solubility of the INH·NA·SA cocrystal and its dissolution rate is comparable to the dissolution rate of the native INH. All other cocrystals showed lower solubility and dissolution rate compared to INH.

Graphical abstract: Novel solid forms of the anti-tuberculosis drug, Isoniazid: ternary and polymorphic cocrystals

Supplementary files

Article information

Article type
Paper
Submitted
26 Apr 2013
Accepted
21 May 2013
First published
22 May 2013

CrystEngComm, 2013,15, 5877-5887

Novel solid forms of the anti-tuberculosis drug, Isoniazid: ternary and polymorphic cocrystals

S. Aitipamula, A. B. H. Wong, P. S. Chow and R. B. H. Tan, CrystEngComm, 2013, 15, 5877 DOI: 10.1039/C3CE40729B

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