Date of Thesis

Summer 2023


Crystallization is a highly stochastic process with numerous contributing variables, and predictable crystal nucleation is still an outstanding challenge. Polymorphism is the tendency of a substance to have more than one solid-state crystalline form. Polymorph- selective crystallization has potential applications in a variety of fields, particularly pharmaceuticals, since the biological availability of an active pharmaceutical ingredient is often polymorph-specific. Different polymorphs also have unique packing between molecules, and it is these structural arrangements that can be utilized in developing surfaces to control crystallization. Heterogenous surface-mediated nucleation is a well-documented phenomenon, wherein crystals preferentially nucleate and grow from chemically similar surfaces. Therefore, the modulation of the surface chemistry of a substrate, such as silica glass, is an attractive avenue to explore for selective polymorph control. Vapor deposition of 3-aminopropyl triethoxysilane yields an amine-terminated surface which can be further modulated using reversible imine protection. This work presents the preparation and characterization of a library of functionalized surfaces and their application in polymorph control. Synthesized surfaces were evaluated in melt recrystallization conditions to target various polymorphs of acetaminophen. By modifying the surface functionality, the polymorph selectivity under recrystallization conditions was transformed. These results demonstrate that surface modification is a viable proof-of-concept process for designing nucleation sites for selective polymorph nucleation.


pharmaceutical, polymorphism, surface chemistry, heterogeneous nucleation, acetaminophen, paracetamol

Access Type

Masters Thesis (Bucknell Access Only)

Degree Type

Master of Science



First Advisor

Dr. Brian J. Smith

Available for download on Wednesday, July 17, 2024