Robust bulk preparation and characterization of sulfamethazine and saccharine salt and cocrystal polymorphs

Sathyanarayana Reddy Perumalla, Chenguang Wang, Yiwang Guo, Limin Shi, Changquan Calvin Sun

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The complex between sulfamethazine and saccharine (SMT-SAC) can exist in two polymorphs, one is a cocrystal and the other is a salt. It is important to fully characterize the two polymorphs for a better understanding of the rare polymorphism between a salt and a cocrystal. However, this effort was hindered by the difficulty in reproducibly preparing a large quantity of phase pure cocrystal polymorph (form II). Here, we developed a method for preparing phase pure cocrystal polymorph robustly by controlling the crystallization medium. Using bulk powders, we determined their free energy diagram, by using intrinsic dissolution rates at 5-37 °C and thermal data near melting temperature. We have shown that the two forms are monotropically related, with the cocrystal form II being more thermodynamically stable up to the melting temperature. We further probed their ionization states based on analyses of the position of protons, bond length, and molecular vibrational motions of pertinent functional groups. Finally, the cocrystal form II exhibited notable differences in moisture sorption and compaction properties, which may influence the choice of solid forms for further development of tablet products.

Original languageEnglish (US)
Pages (from-to)2089-2096
Number of pages8
JournalCrystEngComm
Volume21
Issue number13
DOIs
StatePublished - 2019

Bibliographical note

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© The Royal Society of Chemistry.

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