Graduation Year


Document Type




Degree Granting Department


Major Professor

Michael J. Zaworotko, Ph.D.

Committee Member

Julie P. Harmon, Ph.D.

Committee Member

Abdul Malik, Ph.D.


Polyphenols, Pharmaceutical cocrystals, Hydrogen bond, French paradox, Bioavailability


Crystal engineering is attracting attention in the pharmaceutical industry because the design of new crystal form of drugs can improve their stability, bioavailability and other relevant physical characteristic properties. Therefore, crystal engineering of nutraceuticals such as flavonoids by exploring their hydrogen bonding interactions can generate novel compounds such as pharmaceutical cocrystals. Flavonoids are polyphenolic secondary plant metabolites that are present in varying levels in fruits, vegetables and beverages. The "French paradox", low cardiovascular mortality rate in spite of high intake of saturated fat among the Mediterranean populations made flavonoids an appropriate target for therapeutic researchers.

The work herein deals with the crystal engineering of two flavonoids, quercetin and hesperetin, which are already known to exhibit antioxidant properties and reduce cardiovascular effects in humans. However, they have limited bioavailability and poor water solubility. Several new forms of quercetin and hesperetin in the form of solvates and cocrystals were synthesized. These new crystal forms were characterized by various techniques: FT-IR, DSC (Differential Scanning Calorimetry), single X-ray diffraction, powder X-ray diffraction, TGA (Thermal Gravimetric Analysis) and melting point. The new compounds were also studied via dissolution studies performed in 1:1 ethanol/water (V/V%). Thus, crystal engineering proves to be effective way to enhance the solubility and bioavailability of the target flavonoid molecules.