Graduation Year
2009
Document Type
Dissertation
Degree
Ph.D.
Degree Granting Department
Chemistry
Major Professor
Michael J. Zaworotko, Ph.D.
Committee Member
Mohamed Eddaoudi, Ph.D.
Committee Member
Wayne C. Guida, Ph.D.
Committee Member
Joanna A. Bis, Ph.D.
Keywords
Supramolecular chemistry, Pharmaceutical cocrystal, Crystal form, Crystal engineering, Lamotrigine, Meloxicam
Abstract
With a greater understanding of the fundamentals of crystal engineering lays the
potential for the development of a vast array of novel materials for a plethora of
applications. Addressed herein is the latent potential of the current knowledge base with
an emphasis upon cocrystallization and the desire for scientific exploration that will lead
to the development of a future generation of novel cocrystals. The focus of this
dissertation is to expand the cocrystallization knowledge base in two directions with the
utilization of cocrystals in the novel synthetic technique of cocrystal controlled solid-state
synthesis and in the development of active pharmaceutical ingredients.
Cocrystal controlled solid-state synthesis uses a cocrystal to align the reactive
moieties in such a way that the reaction occurs more quickly and in higher yield than the
typical solution methodology. The focus herein is upon cocrystal controlled solid-state
synthesis of imides where an anhydride and primary amine were the reactive moieties.
Forty-nine reactions were attempted and thirty-two resulted in successful imide
formation. In addition, the cocrystal was isolated as part of the reaction pathway in three
cases and is described in detail.
The impact of cocrystals upon active pharmaceutical ingredients is also addressed
with a focus upon generating novel crystal forms of lamotrigine and meloxicam.
Cocrystallization attempts of lamotrigine resulted in ten novel crystal forms including
three cocrystals, one cocrystal solvate, three salts, one solvated salt, a methanol solvate,
and an ethanol hydrate. Additionally, cocrystallization attempts of meloxicam afforded
seven novel cocrystals. Solubility and pharmacokinetic studies were conducted for a
selected set of lamotrigine and meloxicam crystal forms to determine the crystal form
with the most desirable properties. Properties between crystal form and cocrystal former
were also examined.
Scholar Commons Citation
Cheney, Miranda L., "The Role of Cocrystals in Solid-State Synthesis of Imides and the Development of Novel Crystalline Forms of Active Pharmaceutical Ingredients" (2009). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/3693
