Combining Sodium Profen Salts with Carbohydrates through Ionic Cocrystallization

Crystal engineering techniques that incorporate active pharmaceutical ingredients with sweetening agents present an effective methodology for mitigating the unpleasant taste characteristics of pharmaceutical compounds. Until now, carbohydrates, the natural and most common sweeteners, have rarely been used in taste masking through crystal engineering, probably due to their inability to form salt or unfavorable behavior in cocrystallization. In this study, profens, a series of popular anti-inflammatory drugs that could not be combined with carbohydrates, were transformed into their corresponding sodium salt forms and successfully combined with various carbohydrates through an ionic cocrystallization process, yielding several ionic cocrystals with a similar sandwich-like layered structure. Surprisingly, ionic cocrystallization with xylitol greatly reduced the hygroscopicity of sodium Profen salts. All three sodium Profen-xylitol ionic cocrystals exhibit anhydrous forms with minimal water absorption even under high relative humidity. This study highlights the potential of using carbohydrates as universal coformers with potential future application in taste masking, as well as reducing hygroscopicity issues of pharmaceutical sodium salts, providing valuable insights for drug formulation and stability improvement.