Date of Thesis

Spring 2025

Description

Pharmaceutical drug delivery strongly depends on the solid-state packing of the active pharmaceutical ingredient (API) within a pill or tablet. However, many drugs can form multiple different packing crystal structures, or polymorphs, that are difficult to predict and control. These polymorphs may have different properties such as compressibility, bioavailability, and solubility, which may significantly impact drug pharmacokinetics. Thus, polymorph selectivity has become a vital part of the pharmaceutical development and formulation process. Several factors impact selective polymorph crystallization, including environmental conditions and the use of additives in the polymorph mixture. Acetaminophen, the active ingredient in Tylenol, is an example of a polymorphic compound, with nine polymorphic forms, three of which are well characterized and form at standard temperatures and pressures. Among these three, Form III is of particular interest as it is labeled “elusive” in the literature and has not been prepared as a single crystal to date. Several variables have been proposed to control Form III crystallization, with one recent report highlighting the effectiveness of lactose in promoting Form III. This thesis explores how the model drug acetaminophen crystallizes when different sugar-based additives are present during crystallization. The success of the selective crystallization using heating-cooling cycles was determined via differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). We find that the use of multiple sugar excipients facilitate the crystallization of Form III acetaminophen, although to different extents depending on the sugar used. Fructose and sucrose are observed to have some of the best performance. Additionally, there is a shift in the onset temperature of initial crystallization when sugar additives are used; this effect is most prominent in samples containing monosaccharides. Finally, Form III crystallization with non-sugar additives was demonstrated using silica powder.

Keywords

acetaminophen, crystallization, additive

Access Type

Honors Thesis (Bucknell Access Only)

Degree Type

Bachelor of Science

Major

Cell Biology/Biochemistry

Minor, Emphasis, or Concentration

Philosophy

First Advisor

Brian J Smith

Second Advisor

Hasan Arslan

Third Advisor

Abigail Kopec

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Available for download on Friday, May 14, 2027

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