Creatine is recognized as a dietary staple among athletes, with two supplement formulations currently available on the United States market: creatine monohydrate and creatine hydrochloride. Creatine monohydrate has relatively low aqueous solubility, which hampers its ease of preparation by consumers. Creatine hydrochloride has excellent aqueous solubility; however, it exhibits a strong acidic taste with potentially harmful effects on dental health. Herein, we report a mechanochemical synthesis of a 1:1 coamorphous formulation of creatine and citric acid, a-CCA. Milling of anhydrous creatine and anhydrous citric acid yielded a-CCA, which was found to be structurally stable under dry conditions. Upon exposure to humid air, a-CCA rapidly converted into a 1:1 cocrystalline formulation, c-CCA. Correspondingly, milling of creatine and citric acid, with at least one source present as a monohydrate, resulted in direct mechanosynthesis of the cocrystal. The crystal structure was solved and refined from powder X-ray diffraction data, and the obtained structure solution was evaluated by energy minimization calculations. Close inspection of the hydrogen-bonding network revealed the presence of creatine in zwitterionic form and of citric acid as a neutral molecule. Additionally, the coamorphous solid and the cocrystal were studied by infrared spectroscopy, differential scanning calorimetry, and thermogravimetry. The aqueous solubility of the cocrystal (32.0(8) g/L) was determined to be ∼2.5× higher compared to that of commercial creatine monohydrate (13.3(6) g/L). The cocrystal formulation was determined to be ∼10× less acidic compared to commercial creatine hydrochloride. The simple, efficient, and scalable method of preparation, the phase-purity and high degree of crystallinity under ambient conditions, and the increased solubility (compared to the creatine monohydrate) and decreased acidity (compared to creatine hydrochloride) render the 1:1 creatine:citric acid cocrystal an improved and potentially marketable creatine supplement formulation.

Here we report the phase diagram of acetonitrile and benzene with the focus on a 1 : 3 acetonitrile : benzene cocrystal relevant to mineralogy of Titan, Saturn's moon.

Benzene and acetonitrile are two of the most commonly used solvents found in almost every chemical laboratory. Titan, Saturn’s icy moon, is one other place in the Solar system that has even larger amounts of these compounds, together with many other hydrocarbons. On Titan, organic molecules are produced in the atmosphere and carried by methane rainfall to the surface, where they either dissolve in the lakes, deposit as sandy dunes, or solidify as minerals with complex composition and structure. In order to untangle these structural complexities a reliable model of the phase behavior of these compounds at temperatures relevant to Titan is crucial. We therefore report the composition–temperature binary phase diagram of acetonitrile and benzene, and provide a detailed account of the structure and composition of the phases. This work is based on differential scanning calorimetry and in situ powder diffraction analyses with synchrotron X-ray radiation and supported by theoretical modeling. Benzene and acetonitrile were found to undergo a peritectic reaction into a cocrystal with a 1:3 acetonitrile:benzene stoichiometry. The crystal structure was solved and refined in the polar space group, R3, and the solution was confirmed and optimized by energy minimization calculations. To mimic the environment on Titan more accurately, we tested the stability of the structure under liquid ethane. The diffraction data indicate that the cocrystal undergoes further change upon contact with ethane. These results provide new insights into the structure and stability of a potential mineral on Titan, and contribute to the fundamental knowledge of some of the smallest organic molecules

We report a simple, efficient, and scalable mechanochemical method of preparation of new creatine fitness supplement with increased solubility (compared to the creatine monohydrate) and decreased acidity (compared to creatine hydrochloride).