Sweet Theophylline Cocrystal with Two Tautomers of Acesulfame

A novel pharmaceutical cocrystal (THPAH12) of Theophylline (THP) was obtained with an artificial sweetener, Acesulfame (AH), in a molar ratio of 1:2. Solid state NMR spectra of the cocrystal indicate that the two AH molecules exist as keto and enol tautomers, which is further confirmed by the refined crystal structure. THPAH12 is the first keto form AH containing cocrystal. This highlights the fact that not only −OH of enol form of AH, but also the −NH–CO group of the keto form of AH should be considered when designing new pharmaceutical cocrystals via the supramolecular synthon approach. Compared with pure THP, THPAH12 possesses enhanced solubility and hydration stability, which highlight its potential for further pharmaceutical applications.