Graduation Year


Document Type




Degree Granting Department


Major Professor

Michael J. Zaworotko, Ph.D.

Committee Member

Mohamed Eddaoudi, Ph.D.

Committee Member

Abdul Malik, Ph.D.


Supramolecular Chemistry, Cambridge Structural Database, Hydrogen Bond, Resveratrol, Polymorphism


The work presented herein focus upon crystal engineering of nutraceutical cocrystals. Cocrystals are considered unique solid dosage form which has many advantages over other traditionally known solid forms. Furthermore, cocrystals have proven to improve stability, solubility and bioavailability of Active Pharmaceutical Ingredient (API) as shown in the case of carbamazepine and other APIs in previous studies.

Crystal engineering is commonly used to design new solid forms based on the bases of supramolecular chemistry. In this study, crystal engineering based on intensive Cambridge Structural Database (CSD) analysis used to predict and design new cocrystals of targeted nutraceuticals. Two nutraceuticals were selected for this study; resveratrol and citric acid. The rationale behind selecting resveratrol was to improve its solubility and, accordingly, bioavailability. On the other hand, citric acid is known as a highly soluble and safe nutraceutical, and thus it can be used as a coformer. Five new cocrystals were prepared and characterized using a variety of techniques that include single crystal X-ray diffraction (XRD), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), FT-IR, and thermo-gravimetric analysis (TGA). Most of the reported cocrystals were obtained using different techniques; solvent slow evaporation, mechanichemical approach, slurry, and from melt. Moreover, dissolution test has been performed on resveratrol and two of its cocrystals, using UV-vis spectrophotometer, where the data demonstrate that through cocrystallization with different cocrystal formers, solubility of resveratrol could be greatly modified, and further controlled.

The polymorphism phenomenon is encountered, and accordingly addressed, herein where four novel polymorphs were obtained during cocrystallization attempts. Polymorphism has a significant importance in industry, in general, and in pharmaceutical industry, in particular, due to the vast differences in physical properties of polymorphs. Furthermore, the study of polymorphism provides valuable information essential to understand how different crystal forms are attained.