Role of Coformer and Excipient Properties on the Solid-State Stability of Theophylline Cocrystals

Sampada Koranne, Joseph F. Krzyzaniak, Suman Luthra, Kapildev K. Arora, Raj Suryanarayanan

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The stability of theophylline cocrystals composed of acidic (glutaric acid), basic (isonicotinamide), or neutral (benzamide) coformers was evaluated in the presence of several excipients. Tablets of theophylline-glutaric acid (TG) and theophylline-isonicotinamide (TINT) cocrystals were stable "as is" (no excipient) after storage at 40 °C/75% RH for 1 week. However, TG and TINT cocrystals dissociated rapidly in the presence of basic and acidic excipients, respectively. The dissociation reaction was water-mediated, and theophylline, the reaction product, was identified by powder X-ray diffractometry. In the case of theophylline-benzamide cocrystal, storage of tablets with and without excipients at 40 °C/75% RH for 1 week resulted in a cocrystal polymorphic transformation. Thus, the potential for excipient-induced cocrystal dissociation exists for cocrystals composed of acidic and basic coformers. Moreover, if the coformer renders the cocrystal highly water-soluble, even in the presence of neutral excipients, there is a propensity for dissociation.

Original languageEnglish (US)
Pages (from-to)868-875
Number of pages8
JournalCrystal Growth and Design
Volume19
Issue number2
DOIs
StatePublished - Feb 6 2019

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