Date of Thesis

Spring 2023


Polymorphism is the ability for a molecule to crystallize into multiple different structures in the solid state. The preparation of one polymorph over another is practically important to pharmaceutical development, as properties of polymorphs can vary and impact the drug delivery method. Polymorph outcomes depend heavily on the environment in which the crystal is nucleated, or initially formed. Acetaminophen, the active ingredient in Tylenol, is one example of a polymorphic compound. Here we use acetaminophen as a model system to better understand primary factors controlling polymorph selection and interconversion. We hypothesize a specific atmospheric environmental factor plays large role in the polymorph selectivity of acetaminophen nucleation in melt recrystallization. To explore this, we crystallize acetaminophen under various atmospheric conditions and used differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) to characterize the process. The resulting data revealed that the polymorphs of acetaminophen that are often reported in the literature as “elusive” can be reproducibly crystallized through melt recrystallization when the atmospheric headspace is controlled for humidity. Specifically, when melt recrystallization of acetaminophen occurs in the presence of humidity it generates the Form II polymorph, and in the absence of humidity, the Form III polymorph. With humidity isolated as the controlling factor, further exploration into the levels of humidity can give us a better understanding of polymorphism selectivity.


Polymorphism, acetaminophen, crystallization

Access Type

Honors Thesis

Degree Type

Bachelor of Science


Cell Biology/Biochemistry

First Advisor

Brian Smith

Second Advisor

David Rovnyak

Third Advisor

Kenneth Mineart

Included in

Chemistry Commons